HAEM5:Acute myeloid leukaemia with BCR::ABL1 fusion - Revision history

Bailey.Glen at 17:06, 3 July 2025

2025-07-03T17:06:11Z

← Older revision		Revision as of 12:06, 3 July 2025
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	\|}		\|}

	~~==WHO Essential and Desirable Genetic Diagnostic Criteria==~~
	~~{\| class="wikitable"~~
	\|+
	\|WHO Essential Criteria (Genetics)*
	~~\|Detection of ''BCR::ABL1'' at initial diagnosis.~~
	\|-
	\|WHO Desirable Criteria (Genetics)*
	\|Presence of t(9;22)(q34;q11.2) on conventional karyotyping; determination of the ''BCR::ABL1'' transcript subtype and establishment of a baseline level of ''BCR::ABL1'' transcript subtype and establishment of a baseline level of ''BCR::ABL1'' transcript for monitoring treatment response.
	\|-
	~~\|Other Classification~~
	~~\|N/A~~
	\|}
	<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
	==Related Terminology==		==Related Terminology==

Jennelleh at 15:09, 28 May 2025

2025-05-28T15:09:06Z

← Older revision		Revision as of 10:09, 28 May 2025
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	\|-		\|-
	\|Other Classification		\|Other Classification
	\|		\|N/A
	\|}		\|}
	<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].		<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].

Jennelleh at 15:07, 28 May 2025

2025-05-28T15:07:22Z

← Older revision		Revision as of 10:07, 28 May 2025
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	{{DISPLAYTITLE:Acute myeloid leukaemia with BCR::ABL1 fusion}}		{{DISPLAYTITLE:Acute myeloid leukaemia with BCR::ABL1 fusion}}

	[[HAEM5:Table_of_Contents\|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]		[[HAEM5:Table_of_Contents\|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]

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	\|+		\|+
	\|WHO Essential Criteria (Genetics)*		\|WHO Essential Criteria (Genetics)*
	\|~~a myeloid neoplasm with >20% blasts expressing a myeloid immunophenotype in the bone marrow and/or peripheral blood; detection~~ of ''BCR::ABL1'' at initial diagnosis~~; lack of features of chronic myeloid leukaemia (CML) before or at diagnosis or after therapy~~.		\|Detection of ''BCR::ABL1'' at initial diagnosis.
	\|-		\|-
	\|WHO Desirable Criteria (Genetics)*		\|WHO Desirable Criteria (Genetics)*
	\|~~presence~~ of t(9;22)(q34;q11.2) on conventional karyotyping; determination of the ''BCR::ABL1'' transcript subtype and establishment of a baseline level of ''BCR::ABL1'' transcript subtype and establishment of a baseline level of ''BCR::ABL1'' transcript for monitoring treatment response.		\|Presence of t(9;22)(q34;q11.2) on conventional karyotyping; determination of the ''BCR::ABL1'' transcript subtype and establishment of a baseline level of ''BCR::ABL1'' transcript subtype and establishment of a baseline level of ''BCR::ABL1'' transcript for monitoring treatment response.
	\|-		\|-
	\|Other Classification		\|Other Classification

Bailey.Glen at 21:25, 25 May 2025

2025-05-25T21:25:35Z

← Older revision		Revision as of 16:25, 25 May 2025
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	\|t(9;22)(q34;q11.2)		\|t(9;22)(q34;q11.2)
	\|Common (CML); Rare (AML).<!-- The new version WHO indicates BCR::ABL1 is rare in AML, only accounts less than 0.5%, but the literature I found typically is 0.5-3%, the previous version also indicates the prevalence is <3%. Pls advice which number I should use. -->		\|Common (CML); Rare (AML).<!-- The new version WHO indicates BCR::ABL1 is rare in AML, only accounts less than 0.5%, but the literature I found typically is 0.5-3%, the previous version also indicates the prevalence is <3%. Pls advice which number I should use. -->
	\|~~'''~~Diagnosis:~~'''~~ BCR-ABL1 positive AML is an emerging entity. The proliferation of ''BCR-ABL1'' positive blasts present a diagnostic dilemma. While it may be difficult, it is essential to distinguish between BCR-ABL1 positive AML and Chronic Myeloid Leukemia in Myeloid Blast Crisis (CML-MBC), in order to choose the most appropriate therapy (e.g., intensive induction chemotherapy versus tyrosine kinase inhibitor (TKI) followed by an early allogeneic stem cell transplant). After the exclusion of acute leukemia of ambiguous lineage (a separate entity according to WHO) by flow cytometry, it is helpful to note any past history of antecedent hematological disease. Compared to CML-MBC, a higher percentage of blasts (median: 47% vs 13%), a lower percentage of basophils (median: 0% vs 2.5%) and absolute basophil count, a lower frequency of splenomegaly (25% vs 65%), lower cellularity, fewer dwarf megakaryocytes, and normal M:E ratio favor the diagnosis of BCR-ABL1 positive AML<ref name=":4" /><ref name=":3" />. The detection of p190 transcript and the occurrence of any BCR-ABL1 transcript in less than 100% of metaphases supports the diagnosis of AML rather than CML. Persistent CCyR (Complete Cytogenetic Response) after conventional chemotherapy is unusual for CML-MBC and supports the diagnosis of BCR-ABL1 positive AML<ref name=":2" />. Karyotype analysis that identifies the t(9;22)(q34;q11.2) translocation, either alone or in conjunction with additional chromosomal abnormalities, characterizes BCR-ABL1 positive AML<ref name=":3" /><ref name=":4" />. In addition, molecular methods including dual-colour dual-fusion FISH, RT-PCR, qPCR, and RNA or DNA sequencing are used to identify all common breakpoint variants when applicable.		\|Diagnosis: BCR-ABL1 positive AML is an emerging entity. The proliferation of ''BCR-ABL1'' positive blasts present a diagnostic dilemma. While it may be difficult, it is essential to distinguish between BCR-ABL1 positive AML and Chronic Myeloid Leukemia in Myeloid Blast Crisis (CML-MBC), in order to choose the most appropriate therapy (e.g., intensive induction chemotherapy versus tyrosine kinase inhibitor (TKI) followed by an early allogeneic stem cell transplant). After the exclusion of acute leukemia of ambiguous lineage (a separate entity according to WHO) by flow cytometry, it is helpful to note any past history of antecedent hematological disease. Compared to CML-MBC, a higher percentage of blasts (median: 47% vs 13%), a lower percentage of basophils (median: 0% vs 2.5%) and absolute basophil count, a lower frequency of splenomegaly (25% vs 65%), lower cellularity, fewer dwarf megakaryocytes, and normal M:E ratio favor the diagnosis of BCR-ABL1 positive AML<ref name=":4" /><ref name=":3" />. The detection of p190 transcript and the occurrence of any BCR-ABL1 transcript in less than 100% of metaphases supports the diagnosis of AML rather than CML. Persistent CCyR (Complete Cytogenetic Response) after conventional chemotherapy is unusual for CML-MBC and supports the diagnosis of BCR-ABL1 positive AML<ref name=":2" />. Karyotype analysis that identifies the t(9;22)(q34;q11.2) translocation, either alone or in conjunction with additional chromosomal abnormalities, characterizes BCR-ABL1 positive AML<ref name=":3" /><ref name=":4" />. In addition, molecular methods including dual-colour dual-fusion FISH, RT-PCR, qPCR, and RNA or DNA sequencing are used to identify all common breakpoint variants when applicable.


	~~'''~~Prognosis:~~'''~~ The overall prognosis of BCR-ABL1 positive AML is poor, with a median survival time of <9 months<ref>{{Cite journal\|last=Cuneo\|first=A.\|last2=Ferrant\|first2=A.\|last3=Michaux\|first3=J. L.\|last4=Demuynck\|first4=H.\|last5=Boogaerts\|first5=M.\|last6=Louwagie\|first6=A.\|last7=Doyen\|first7=C.\|last8=Stul\|first8=M.\|last9=Cassiman\|first9=J. J.\|date=1996\|title=Philadelphia chromosome-positive acute myeloid leukemia: cytoimmunologic and cytogenetic features\|url=https://pubmed.ncbi.nlm.nih.gov/8952155\|journal=Haematologica\|volume=81\|issue=5\|pages=423–427\|issn=0390-6078\|pmid=8952155}}</ref><ref name=":3" />. The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for AML categorize this entity into the poor-risk group, comparable with complex aberrant karyotype AML<ref name=":6">Pollyea DA, Altman JK, (2025). NCCN Clinical Practice Guidelines in Oncology: AML. Version 2. Available at: NCCN.org.</ref>. It appears that the prognosis of BCR-ABL1 positive AML depends more on the genetic background (concurrent aberrations) than on BCR-ABL1 itself. Unlike in CML, BCR-ABL1 does not appear to be the key driver in AML though may provide a proliferative advantage to a particular BCR-ABL1 positive subclone.		Prognosis: The overall prognosis of BCR-ABL1 positive AML is poor, with a median survival time of <9 months<ref>{{Cite journal\|last=Cuneo\|first=A.\|last2=Ferrant\|first2=A.\|last3=Michaux\|first3=J. L.\|last4=Demuynck\|first4=H.\|last5=Boogaerts\|first5=M.\|last6=Louwagie\|first6=A.\|last7=Doyen\|first7=C.\|last8=Stul\|first8=M.\|last9=Cassiman\|first9=J. J.\|date=1996\|title=Philadelphia chromosome-positive acute myeloid leukemia: cytoimmunologic and cytogenetic features\|url=https://pubmed.ncbi.nlm.nih.gov/8952155\|journal=Haematologica\|volume=81\|issue=5\|pages=423–427\|issn=0390-6078\|pmid=8952155}}</ref><ref name=":3" />. The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for AML categorize this entity into the poor-risk group, comparable with complex aberrant karyotype AML<ref name=":6">Pollyea DA, Altman JK, (2025). NCCN Clinical Practice Guidelines in Oncology: AML. Version 2. Available at: NCCN.org.</ref>. It appears that the prognosis of BCR-ABL1 positive AML depends more on the genetic background (concurrent aberrations) than on BCR-ABL1 itself. Unlike in CML, BCR-ABL1 does not appear to be the key driver in AML though may provide a proliferative advantage to a particular BCR-ABL1 positive subclone.


	~~'''~~Therapeutics:~~'''~~ There is currently no standardized treatment approach for BCR-ABL1 positive AML. Therapy with TKI alone does not produce sustained responses in BCR-ABL1 positive AML<ref name=":3" />. This may be due to a very rapid clonal evolution, resulting in resistance in a much higher proportion of patients and in a significantly shorter time than in CML<ref name=":2" />.Venetoclax and TKI combination regimens have shown good response in some studies<ref>{{Cite journal\|last=Maiti\|first=Abhishek\|last2=Franquiz\|first2=Miguel J.\|last3=Ravandi\|first3=Farhad\|last4=Cortes\|first4=Jorge E.\|last5=Jabbour\|first5=Elias J.\|last6=Sasaki\|first6=Koji\|last7=Marx\|first7=Kayleigh\|last8=Daver\|first8=Naval G.\|last9=Kadia\|first9=Tapan M.\|date=2020\|title=Venetoclax and BCR-ABL Tyrosine Kinase Inhibitor Combinations: Outcome in Patients with Philadelphia Chromosome-Positive Advanced Myeloid Leukemias\|url=https://pubmed.ncbi.nlm.nih.gov/32289808\|journal=Acta Haematologica\|volume=143\|issue=6\|pages=567–573\|doi=10.1159/000506346\|issn=1421-9662\|pmc=7839068\|pmid=32289808}}</ref>.		Therapeutics: There is currently no standardized treatment approach for BCR-ABL1 positive AML. Therapy with TKI alone does not produce sustained responses in BCR-ABL1 positive AML<ref name=":3" />. This may be due to a very rapid clonal evolution, resulting in resistance in a much higher proportion of patients and in a significantly shorter time than in CML<ref name=":2" />.Venetoclax and TKI combination regimens have shown good response in some studies<ref>{{Cite journal\|last=Maiti\|first=Abhishek\|last2=Franquiz\|first2=Miguel J.\|last3=Ravandi\|first3=Farhad\|last4=Cortes\|first4=Jorge E.\|last5=Jabbour\|first5=Elias J.\|last6=Sasaki\|first6=Koji\|last7=Marx\|first7=Kayleigh\|last8=Daver\|first8=Naval G.\|last9=Kadia\|first9=Tapan M.\|date=2020\|title=Venetoclax and BCR-ABL Tyrosine Kinase Inhibitor Combinations: Outcome in Patients with Philadelphia Chromosome-Positive Advanced Myeloid Leukemias\|url=https://pubmed.ncbi.nlm.nih.gov/32289808\|journal=Acta Haematologica\|volume=143\|issue=6\|pages=567–573\|doi=10.1159/000506346\|issn=1421-9662\|pmc=7839068\|pmid=32289808}}</ref>.
	\|Yes (WHO, NCCN)		\|Yes (WHO, NCCN)
	\|The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context<ref>{{Cite journal\|last=Cross\|first=Nicholas C. P.\|last2=Ernst\|first2=Thomas\|last3=Branford\|first3=Susan\|last4=Cayuela\|first4=Jean-Michel\|last5=Deininger\|first5=Michael\|last6=Fabarius\|first6=Alice\|last7=Kim\|first7=Dennis Dong Hwan\|last8=Machova Polakova\|first8=Katerina\|last9=Radich\|first9=Jerald P.\|date=2023-11\|title=European LeukemiaNet laboratory recommendations for the diagnosis and management of chronic myeloid leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/37794101\|journal=Leukemia\|volume=37\|issue=11\|pages=2150–2167\|doi=10.1038/s41375-023-02048-y\|issn=1476-5551\|pmc=10624636\|pmid=37794101}}</ref><ref>{{Cite journal\|last=Sawyers\|first=C. L.\|date=1999-04-29\|title=Chronic myeloid leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/10219069\|journal=The New England Journal of Medicine\|volume=340\|issue=17\|pages=1330–1340\|doi=10.1056/NEJM199904293401706\|issn=0028-4793\|pmid=10219069}}</ref>. The prevalence of BCR"" ABL1 in CML is common ~90-95%<ref>{{Cite journal\|last=Sharma\|first=Diwakar\|last2=Wilson\|first2=Christine\|last3=Kumar\|first3=Sachin\|last4=Ghose\|first4=Sampa\|last5=Sahoo\|first5=Ranjit\|last6=Sharawat\|first6=Surender K.\|date=2024-08-01\|title=Does presence of complex translocations involving BCR::ABL1 in chronic myeloid leukemia affect the response rate to tyrosine kinase inhibitors? A systematic review of the literature\|url=https://linkinghub.elsevier.com/retrieve/pii/S1092913424000406\|journal=Annals of Diagnostic Pathology\|volume=71\|pages=152303\|doi=10.1016/j.anndiagpath.2024.152303\|issn=1092-9134}}</ref>. This fusion is responsive to targeted therapy such as Imatinib (Gleevec)<ref>{{Cite journal\|last=Cortes\|first=Jorge E.\|last2=Talpaz\|first2=Moshe\|last3=Giles\|first3=Francis\|last4=O'Brien\|first4=Susan\|last5=Rios\|first5=Mary Beth\|last6=Shan\|first6=Jianqin\|last7=Garcia-Manero\|first7=Guillermo\|last8=Faderl\|first8=Stefan\|last9=Thomas\|first9=Deborah A.\|date=2003-05-15\|title=Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy\|url=https://pubmed.ncbi.nlm.nih.gov/12560227\|journal=Blood\|volume=101\|issue=10\|pages=3794–3800\|doi=10.1182/blood-2002-09-2790\|issn=0006-4971\|pmid=12560227}}</ref>.		\|The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context<ref>{{Cite journal\|last=Cross\|first=Nicholas C. P.\|last2=Ernst\|first2=Thomas\|last3=Branford\|first3=Susan\|last4=Cayuela\|first4=Jean-Michel\|last5=Deininger\|first5=Michael\|last6=Fabarius\|first6=Alice\|last7=Kim\|first7=Dennis Dong Hwan\|last8=Machova Polakova\|first8=Katerina\|last9=Radich\|first9=Jerald P.\|date=2023-11\|title=European LeukemiaNet laboratory recommendations for the diagnosis and management of chronic myeloid leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/37794101\|journal=Leukemia\|volume=37\|issue=11\|pages=2150–2167\|doi=10.1038/s41375-023-02048-y\|issn=1476-5551\|pmc=10624636\|pmid=37794101}}</ref><ref>{{Cite journal\|last=Sawyers\|first=C. L.\|date=1999-04-29\|title=Chronic myeloid leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/10219069\|journal=The New England Journal of Medicine\|volume=340\|issue=17\|pages=1330–1340\|doi=10.1056/NEJM199904293401706\|issn=0028-4793\|pmid=10219069}}</ref>. The prevalence of BCR"" ABL1 in CML is common ~90-95%<ref>{{Cite journal\|last=Sharma\|first=Diwakar\|last2=Wilson\|first2=Christine\|last3=Kumar\|first3=Sachin\|last4=Ghose\|first4=Sampa\|last5=Sahoo\|first5=Ranjit\|last6=Sharawat\|first6=Surender K.\|date=2024-08-01\|title=Does presence of complex translocations involving BCR::ABL1 in chronic myeloid leukemia affect the response rate to tyrosine kinase inhibitors? A systematic review of the literature\|url=https://linkinghub.elsevier.com/retrieve/pii/S1092913424000406\|journal=Annals of Diagnostic Pathology\|volume=71\|pages=152303\|doi=10.1016/j.anndiagpath.2024.152303\|issn=1092-9134}}</ref>. This fusion is responsive to targeted therapy such as Imatinib (Gleevec)<ref>{{Cite journal\|last=Cortes\|first=Jorge E.\|last2=Talpaz\|first2=Moshe\|last3=Giles\|first3=Francis\|last4=O'Brien\|first4=Susan\|last5=Rios\|first5=Mary Beth\|last6=Shan\|first6=Jianqin\|last7=Garcia-Manero\|first7=Guillermo\|last8=Faderl\|first8=Stefan\|last9=Thomas\|first9=Deborah A.\|date=2003-05-15\|title=Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy\|url=https://pubmed.ncbi.nlm.nih.gov/12560227\|journal=Blood\|volume=101\|issue=10\|pages=3794–3800\|doi=10.1182/blood-2002-09-2790\|issn=0006-4971\|pmid=12560227}}</ref>.
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	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
	!Chr #!!~~'''~~Gain, Loss, Amp, LOH~~'''~~!!~~'''~~Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]~~'''~~!!~~'''~~Relevant Gene(s)~~'''~~		!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
	!~~'''~~Diagnostic, Prognostic, and Therapeutic Significance - D, P, T~~'''~~		!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
	!~~'''~~Established Clinical Significance Per Guidelines - Yes or No (Source)~~'''~~		!Established Clinical Significance Per Guidelines - Yes or No (Source)
	!~~'''~~Clinical Relevance Details/Other Notes~~'''~~		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|7		\|7
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	!Chromosomal Pattern		!Chromosomal Pattern
	!Molecular Pathogenesis		!Molecular Pathogenesis
	!~~'''~~Prevalence -~~'''~~		!Prevalence -
	~~'''~~Common >20%, Recurrent 5-20% or Rare <5% (Disease)~~'''~~		Common >20%, Recurrent 5-20% or Rare <5% (Disease)
	!~~'''~~Diagnostic, Prognostic, and Therapeutic Significance - D, P, T~~'''~~		!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
	!~~'''~~Established Clinical Significance Per Guidelines - Yes or No (Source)~~'''~~		!Established Clinical Significance Per Guidelines - Yes or No (Source)
	!~~'''~~Clinical Relevance Details/Other Notes~~'''~~		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|inv(16)(p13.1q22) or t(16;16)(p13.1;q22)		\|inv(16)(p13.1q22) or t(16;16)(p13.1;q22)
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	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
	!Gene!!~~'''~~Genetic Alteration~~'''~~!!~~'''~~Tumor Suppressor Gene, Oncogene, Other~~'''~~!!~~'''~~Prevalence -~~'''~~		!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
	~~'''~~Common >20%, Recurrent 5-20% or Rare <5% (Disease)~~'''~~		Common >20%, Recurrent 5-20% or Rare <5% (Disease)
	!~~'''~~Diagnostic, Prognostic, and Therapeutic Significance - D, P, T ~~'''~~		!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
	!~~'''~~Established Clinical Significance Per Guidelines - Yes or No (Source)~~'''~~		!Established Clinical Significance Per Guidelines - Yes or No (Source)
	!~~'''~~Clinical Relevance Details/Other Notes~~'''~~		!Clinical Relevance Details/Other Notes
	\|-		\|-
	\|''RUNX1''		\|''RUNX1''

Bailey.Glen at 20:01, 25 May 2025

2025-05-25T20:01:59Z

← Older revision		Revision as of 15:01, 25 May 2025
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	<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].		<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
	==Related Terminology==		==Related Terminology==

	{\| class="wikitable"		{\| class="wikitable"
	\|+		\|+
	\|Acceptable		\|Acceptable
	\|~~acute~~ myeloid leukaemia with t(9;22)(q34;q11.2)		\|Acute myeloid leukaemia with t(9;22)(q34;q11.2)
	\|-		\|-
	\|Not Recommended		\|Not Recommended
	\|		\|N/A
	\|}		\|}

Bailey.Glen at 19:19, 25 May 2025

2025-05-25T19:19:59Z

← Older revision		Revision as of 14:19, 25 May 2025
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	{{DISPLAYTITLE:Acute myeloid leukaemia with BCR::ABL1 fusion}}		{{DISPLAYTITLE:Acute myeloid leukaemia with BCR::ABL1 fusion}}

	[[HAEM5:Table_of_Contents\|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]		[[HAEM5:Table_of_Contents\|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]

Bailey.Glen at 16:46, 22 May 2025

2025-05-22T16:46:16Z

← Older revision		Revision as of 11:46, 22 May 2025
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	<br />		<br />

	[[File:BCR-ABL1 translocation image.jpg\|Figure 1. Philadelphia chromosome. A piece of chromosome 9 and a piece of chrosomome 22 break off and trade places. The BCR-ABL1 gene is formed on chromosome 22 where the piece of chromosome 9 attaches. The changed chromosome 22 is called Philadelphia chromosome. Image from National Cancer Institute website https://www.cancer.gov/publications/dictionaries/cancer-terms/def/bcr-abl-fusion-gene\|frame\|~~center~~]][[File:Screenshot 2025-05-11 181714.png\|thumb\|Figure 2. Signal transduction pathway of the BCR-ABL fusion gene]]~~<!-- why my figure is not in the middle? LOL --><br />~~		[[File:BCR-ABL1 translocation image.jpg\|Figure 1. Philadelphia chromosome. A piece of chromosome 9 and a piece of chrosomome 22 break off and trade places. The BCR-ABL1 gene is formed on chromosome 22 where the piece of chromosome 9 attaches. The changed chromosome 22 is called Philadelphia chromosome. Image from National Cancer Institute website https://www.cancer.gov/publications/dictionaries/cancer-terms/def/bcr-abl-fusion-gene\|frame\|alt=\|none]][[File:Screenshot 2025-05-11 181714.png\|thumb\|Figure 2. Signal transduction pathway of the BCR-ABL fusion gene\|alt=\|none]]








	==Genetic Diagnostic Testing Methods==		==Genetic Diagnostic Testing Methods==

Bailey.Glen at 16:43, 22 May 2025

2025-05-22T16:43:50Z

← Older revision		Revision as of 11:43, 22 May 2025
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	Survival status postallogeneic transplantation appears similar to intermediate risk AML, with one report demonstrating 3 year overall survival of 73%<ref>{{Cite journal\|last=Konoplev\|first=Sergej\|last2=Yin\|first2=C. Cameron\|last3=Kornblau\|first3=Steven M.\|last4=Kantarjian\|first4=Hagop M.\|last5=Konopleva\|first5=Marina\|last6=Andreeff\|first6=Michael\|last7=Lu\|first7=Gary\|last8=Zuo\|first8=Zhuang\|last9=Luthra\|first9=Rajyalakshmi\|date=2013-01\|title=Molecular characterization of de novo Philadelphia chromosome-positive acute myeloid leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/22691121\|journal=Leukemia & Lymphoma\|volume=54\|issue=1\|pages=138–144\|doi=10.3109/10428194.2012.701739\|issn=1029-2403\|pmc=3925981\|pmid=22691121}}</ref>.		Survival status postallogeneic transplantation appears similar to intermediate risk AML, with one report demonstrating 3 year overall survival of 73%<ref>{{Cite journal\|last=Konoplev\|first=Sergej\|last2=Yin\|first2=C. Cameron\|last3=Kornblau\|first3=Steven M.\|last4=Kantarjian\|first4=Hagop M.\|last5=Konopleva\|first5=Marina\|last6=Andreeff\|first6=Michael\|last7=Lu\|first7=Gary\|last8=Zuo\|first8=Zhuang\|last9=Luthra\|first9=Rajyalakshmi\|date=2013-01\|title=Molecular characterization of de novo Philadelphia chromosome-positive acute myeloid leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/22691121\|journal=Leukemia & Lymphoma\|volume=54\|issue=1\|pages=138–144\|doi=10.3109/10428194.2012.701739\|issn=1029-2403\|pmc=3925981\|pmid=22691121}}</ref>.
	\|}~~<center>~~		\|}
	==Individual Region Genomic Gain/Loss/LOH==		==Individual Region Genomic Gain/Loss/LOH==

Xinxiu.Xu at 22:09, 13 May 2025

2025-05-13T22:09:30Z

← Older revision		Revision as of 17:09, 13 May 2025
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	\|''ABL1''\|\|''BCR::ABL1''\|\|The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.		\|''ABL1''\|\|''BCR::ABL1''\|\|The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.
	\|t(9;22)(q34;q11.2)		\|t(9;22)(q34;q11.2)
	\|Common (CML); Rare (AML)<ref name=":5">{{Cite journal\|last=Al Hamad\|first=Mohammad\|date=2021\|title=Contribution of BCR-ABL molecular variants and leukemic stem cells in response and resistance to tyrosine kinase inhibitors: a review\|url=https://pubmed.ncbi.nlm.nih.gov/35284066\|journal=F1000Research\|volume=10\|pages=1288\|doi=10.12688/f1000research.74570.2\|issn=2046-1402\|pmc=8886173\|pmid=35284066}}</ref>.<!-- The new version WHO indicates BCR::ABL1 is rare in AML, only accounts less than 0.5%, but the literature I found typically is 0.5-3%, the previous version also indicates the prevalence is <3%. Pls advice which number I should use. -->		\|Common (CML); Rare (AML).<!-- The new version WHO indicates BCR::ABL1 is rare in AML, only accounts less than 0.5%, but the literature I found typically is 0.5-3%, the previous version also indicates the prevalence is <3%. Pls advice which number I should use. -->
	\|'''Diagnosis:''' BCR-ABL1 positive AML is an emerging entity. The proliferation of ''BCR-ABL1'' positive blasts present a diagnostic dilemma. While it may be difficult, it is essential to distinguish between BCR-ABL1 positive AML and Chronic Myeloid Leukemia in Myeloid Blast Crisis (CML-MBC), in order to choose the most appropriate therapy (e.g., intensive induction chemotherapy versus tyrosine kinase inhibitor (TKI) followed by an early allogeneic stem cell transplant). After the exclusion of acute leukemia of ambiguous lineage (a separate entity according to WHO) by flow cytometry, it is helpful to note any past history of antecedent hematological disease. Compared to CML-MBC, a higher percentage of blasts (median: 47% vs 13%), a lower percentage of basophils (median: 0% vs 2.5%) and absolute basophil count, a lower frequency of splenomegaly (25% vs 65%), lower cellularity, fewer dwarf megakaryocytes, and normal M:E ratio favor the diagnosis of BCR-ABL1 positive AML<ref name=":4" /><ref name=":3" />. The detection of p190 transcript and the occurrence of any BCR-ABL1 transcript in less than 100% of metaphases supports the diagnosis of AML rather than CML. Persistent CCyR (Complete Cytogenetic Response) after conventional chemotherapy is unusual for CML-MBC and supports the diagnosis of BCR-ABL1 positive AML<ref name=":2" />. Karyotype analysis that identifies the t(9;22)(q34;q11.2) translocation, either alone or in conjunction with additional chromosomal abnormalities, characterizes BCR-ABL1 positive AML<ref name=":3" /><ref name=":4" />. In addition, molecular methods including dual-colour dual-fusion FISH, RT-PCR, qPCR, and RNA or DNA sequencing are used to identify all common breakpoint variants when applicable.		\|'''Diagnosis:''' BCR-ABL1 positive AML is an emerging entity. The proliferation of ''BCR-ABL1'' positive blasts present a diagnostic dilemma. While it may be difficult, it is essential to distinguish between BCR-ABL1 positive AML and Chronic Myeloid Leukemia in Myeloid Blast Crisis (CML-MBC), in order to choose the most appropriate therapy (e.g., intensive induction chemotherapy versus tyrosine kinase inhibitor (TKI) followed by an early allogeneic stem cell transplant). After the exclusion of acute leukemia of ambiguous lineage (a separate entity according to WHO) by flow cytometry, it is helpful to note any past history of antecedent hematological disease. Compared to CML-MBC, a higher percentage of blasts (median: 47% vs 13%), a lower percentage of basophils (median: 0% vs 2.5%) and absolute basophil count, a lower frequency of splenomegaly (25% vs 65%), lower cellularity, fewer dwarf megakaryocytes, and normal M:E ratio favor the diagnosis of BCR-ABL1 positive AML<ref name=":4" /><ref name=":3" />. The detection of p190 transcript and the occurrence of any BCR-ABL1 transcript in less than 100% of metaphases supports the diagnosis of AML rather than CML. Persistent CCyR (Complete Cytogenetic Response) after conventional chemotherapy is unusual for CML-MBC and supports the diagnosis of BCR-ABL1 positive AML<ref name=":2" />. Karyotype analysis that identifies the t(9;22)(q34;q11.2) translocation, either alone or in conjunction with additional chromosomal abnormalities, characterizes BCR-ABL1 positive AML<ref name=":3" /><ref name=":4" />. In addition, molecular methods including dual-colour dual-fusion FISH, RT-PCR, qPCR, and RNA or DNA sequencing are used to identify all common breakpoint variants when applicable.

Line 86:		Line 86:
	BCR::ABL1 is generally favorable in CML<ref>{{Cite journal\|last=Branford\|first=Susan\|last2=Yeung\|first2=David T.\|last3=Parker\|first3=Wendy T.\|last4=Roberts\|first4=Nicola D.\|last5=Purins\|first5=Leanne\|last6=Braley\|first6=Jodi A.\|last7=Altamura\|first7=Haley K.\|last8=Yeoman\|first8=Alexandra L.\|last9=Georgievski\|first9=Jasmina\|date=2014-07-24\|title=Prognosis for patients with CML and >10% BCR-ABL1 after 3 months of imatinib depends on the rate of BCR-ABL1 decline\|url=https://pubmed.ncbi.nlm.nih.gov/24859364\|journal=Blood\|volume=124\|issue=4\|pages=511–518\|doi=10.1182/blood-2014-03-566323\|issn=1528-0020\|pmid=24859364}}</ref><ref>{{Cite journal\|last=Lauseker\|first=Michael\|last2=Hehlmann\|first2=Rüdiger\|last3=Hochhaus\|first3=Andreas\|last4=Saußele\|first4=Susanne\|date=2023-11\|title=Survival with chronic myeloid leukaemia after failing milestones\|url=https://pubmed.ncbi.nlm.nih.gov/37726340\|journal=Leukemia\|volume=37\|issue=11\|pages=2231–2236\|doi=10.1038/s41375-023-02028-2\|issn=1476-5551\|pmc=10624616\|pmid=37726340}}</ref>.		BCR::ABL1 is generally favorable in CML<ref>{{Cite journal\|last=Branford\|first=Susan\|last2=Yeung\|first2=David T.\|last3=Parker\|first3=Wendy T.\|last4=Roberts\|first4=Nicola D.\|last5=Purins\|first5=Leanne\|last6=Braley\|first6=Jodi A.\|last7=Altamura\|first7=Haley K.\|last8=Yeoman\|first8=Alexandra L.\|last9=Georgievski\|first9=Jasmina\|date=2014-07-24\|title=Prognosis for patients with CML and >10% BCR-ABL1 after 3 months of imatinib depends on the rate of BCR-ABL1 decline\|url=https://pubmed.ncbi.nlm.nih.gov/24859364\|journal=Blood\|volume=124\|issue=4\|pages=511–518\|doi=10.1182/blood-2014-03-566323\|issn=1528-0020\|pmid=24859364}}</ref><ref>{{Cite journal\|last=Lauseker\|first=Michael\|last2=Hehlmann\|first2=Rüdiger\|last3=Hochhaus\|first3=Andreas\|last4=Saußele\|first4=Susanne\|date=2023-11\|title=Survival with chronic myeloid leukaemia after failing milestones\|url=https://pubmed.ncbi.nlm.nih.gov/37726340\|journal=Leukemia\|volume=37\|issue=11\|pages=2231–2236\|doi=10.1038/s41375-023-02028-2\|issn=1476-5551\|pmc=10624616\|pmid=37726340}}</ref>.

	Three BCR-ABL chimeric proteins result from varying mRNA fusions of the ABL and BCR genes. The most common breakpoint occurs in BCR intron 13 or 14, fusing to ABL1 exon a2 (e13a2, e14a2), yielding a 210 kilodalton protein (p210 BCR-ABL1) found in 95% of CML cases. A rare alternative (<1%) is the e19a2 fusion, producing a 230 kilodalton protein (p230 BCR-ABL1), a marker for neutrophilic-chronic myeloid leukemia. The e1a2 fusion results in the p190 BCR-ABL1 protein, prevalent in B cell ALL, less common in AML, and rare in CML<ref name=":5" />.		Three BCR-ABL chimeric proteins result from varying mRNA fusions of the ABL and BCR genes. The most common breakpoint occurs in BCR intron 13 or 14, fusing to ABL1 exon a2 (e13a2, e14a2), yielding a 210 kilodalton protein (p210 BCR-ABL1) found in 95% of CML cases. A rare alternative (<1%) is the e19a2 fusion, producing a 230 kilodalton protein (p230 BCR-ABL1), a marker for neutrophilic-chronic myeloid leukemia. The e1a2 fusion results in the p190 BCR-ABL1 protein, prevalent in B cell ALL, less common in AML, and rare in CML<ref name=":5">{{Cite journal\|last=Al Hamad\|first=Mohammad\|date=2021\|title=Contribution of BCR-ABL molecular variants and leukemic stem cells in response and resistance to tyrosine kinase inhibitors: a review\|url=https://pubmed.ncbi.nlm.nih.gov/35284066\|journal=F1000Research\|volume=10\|pages=1288\|doi=10.12688/f1000research.74570.2\|issn=2046-1402\|pmc=8886173\|pmid=35284066}}</ref>.

Xinxiu.Xu at 22:09, 13 May 2025

2025-05-13T22:09:04Z

← Older revision		Revision as of 17:09, 13 May 2025
Line 72:		Line 72:
	\|''ABL1''\|\|''BCR::ABL1''\|\|The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.		\|''ABL1''\|\|''BCR::ABL1''\|\|The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.
	\|t(9;22)(q34;q11.2)		\|t(9;22)(q34;q11.2)
	\|Common ~~~90-95%~~ (CML)<ref>{{Cite journal\|last=Sharma\|first=Diwakar\|last2=Wilson\|first2=Christine\|last3=Kumar\|first3=Sachin\|last4=Ghose\|first4=Sampa\|last5=Sahoo\|first5=Ranjit\|last6=Sharawat\|first6=Surender K.\|date=2024-08-01\|title=Does presence of complex translocations involving BCR::ABL1 in chronic myeloid leukemia affect the response rate to tyrosine kinase inhibitors? A systematic review of the literature\|url=https://linkinghub.elsevier.com/retrieve/pii/S1092913424000406\|journal=Annals of Diagnostic Pathology\|volume=71\|pages=152303\|doi=10.1016/j.anndiagpath.2024.152303\|issn=1092-9134}}</ref>; Rare ~~~0.5 - 3%~~ (AML)<ref name=":5">{{Cite journal\|last=Al Hamad\|first=Mohammad\|date=2021\|title=Contribution of BCR-ABL molecular variants and leukemic stem cells in response and resistance to tyrosine kinase inhibitors: a review\|url=https://pubmed.ncbi.nlm.nih.gov/35284066\|journal=F1000Research\|volume=10\|pages=1288\|doi=10.12688/f1000research.74570.2\|issn=2046-1402\|pmc=8886173\|pmid=35284066}}</ref>.<!-- The new version WHO indicates BCR::ABL1 is rare in AML, only accounts less than 0.5%, but the literature I found typically is 0.5-3%, the previous version also indicates the prevalence is <3%. Pls advice which number I should use. -->		\|Common (CML); Rare (AML)<ref name=":5">{{Cite journal\|last=Al Hamad\|first=Mohammad\|date=2021\|title=Contribution of BCR-ABL molecular variants and leukemic stem cells in response and resistance to tyrosine kinase inhibitors: a review\|url=https://pubmed.ncbi.nlm.nih.gov/35284066\|journal=F1000Research\|volume=10\|pages=1288\|doi=10.12688/f1000research.74570.2\|issn=2046-1402\|pmc=8886173\|pmid=35284066}}</ref>.<!-- The new version WHO indicates BCR::ABL1 is rare in AML, only accounts less than 0.5%, but the literature I found typically is 0.5-3%, the previous version also indicates the prevalence is <3%. Pls advice which number I should use. -->
	\|'''Diagnosis:''' BCR-ABL1 positive AML is an emerging entity. The proliferation of ''BCR-ABL1'' positive blasts present a diagnostic dilemma. While it may be difficult, it is essential to distinguish between BCR-ABL1 positive AML and Chronic Myeloid Leukemia in Myeloid Blast Crisis (CML-MBC), in order to choose the most appropriate therapy (e.g., intensive induction chemotherapy versus tyrosine kinase inhibitor (TKI) followed by an early allogeneic stem cell transplant). After the exclusion of acute leukemia of ambiguous lineage (a separate entity according to WHO) by flow cytometry, it is helpful to note any past history of antecedent hematological disease. Compared to CML-MBC, a higher percentage of blasts (median: 47% vs 13%), a lower percentage of basophils (median: 0% vs 2.5%) and absolute basophil count, a lower frequency of splenomegaly (25% vs 65%), lower cellularity, fewer dwarf megakaryocytes, and normal M:E ratio favor the diagnosis of BCR-ABL1 positive AML<ref name=":4" /><ref name=":3" />. The detection of p190 transcript and the occurrence of any BCR-ABL1 transcript in less than 100% of metaphases supports the diagnosis of AML rather than CML. Persistent CCyR (Complete Cytogenetic Response) after conventional chemotherapy is unusual for CML-MBC and supports the diagnosis of BCR-ABL1 positive AML<ref name=":2" />. Karyotype analysis that identifies the t(9;22)(q34;q11.2) translocation, either alone or in conjunction with additional chromosomal abnormalities, characterizes BCR-ABL1 positive AML<ref name=":3" /><ref name=":4" />. In addition, molecular methods including dual-colour dual-fusion FISH, RT-PCR, qPCR, and RNA or DNA sequencing are used to identify all common breakpoint variants when applicable.		\|'''Diagnosis:''' BCR-ABL1 positive AML is an emerging entity. The proliferation of ''BCR-ABL1'' positive blasts present a diagnostic dilemma. While it may be difficult, it is essential to distinguish between BCR-ABL1 positive AML and Chronic Myeloid Leukemia in Myeloid Blast Crisis (CML-MBC), in order to choose the most appropriate therapy (e.g., intensive induction chemotherapy versus tyrosine kinase inhibitor (TKI) followed by an early allogeneic stem cell transplant). After the exclusion of acute leukemia of ambiguous lineage (a separate entity according to WHO) by flow cytometry, it is helpful to note any past history of antecedent hematological disease. Compared to CML-MBC, a higher percentage of blasts (median: 47% vs 13%), a lower percentage of basophils (median: 0% vs 2.5%) and absolute basophil count, a lower frequency of splenomegaly (25% vs 65%), lower cellularity, fewer dwarf megakaryocytes, and normal M:E ratio favor the diagnosis of BCR-ABL1 positive AML<ref name=":4" /><ref name=":3" />. The detection of p190 transcript and the occurrence of any BCR-ABL1 transcript in less than 100% of metaphases supports the diagnosis of AML rather than CML. Persistent CCyR (Complete Cytogenetic Response) after conventional chemotherapy is unusual for CML-MBC and supports the diagnosis of BCR-ABL1 positive AML<ref name=":2" />. Karyotype analysis that identifies the t(9;22)(q34;q11.2) translocation, either alone or in conjunction with additional chromosomal abnormalities, characterizes BCR-ABL1 positive AML<ref name=":3" /><ref name=":4" />. In addition, molecular methods including dual-colour dual-fusion FISH, RT-PCR, qPCR, and RNA or DNA sequencing are used to identify all common breakpoint variants when applicable.

Line 81:		Line 81:
	'''Therapeutics:''' There is currently no standardized treatment approach for BCR-ABL1 positive AML. Therapy with TKI alone does not produce sustained responses in BCR-ABL1 positive AML<ref name=":3" />. This may be due to a very rapid clonal evolution, resulting in resistance in a much higher proportion of patients and in a significantly shorter time than in CML<ref name=":2" />.Venetoclax and TKI combination regimens have shown good response in some studies<ref>{{Cite journal\|last=Maiti\|first=Abhishek\|last2=Franquiz\|first2=Miguel J.\|last3=Ravandi\|first3=Farhad\|last4=Cortes\|first4=Jorge E.\|last5=Jabbour\|first5=Elias J.\|last6=Sasaki\|first6=Koji\|last7=Marx\|first7=Kayleigh\|last8=Daver\|first8=Naval G.\|last9=Kadia\|first9=Tapan M.\|date=2020\|title=Venetoclax and BCR-ABL Tyrosine Kinase Inhibitor Combinations: Outcome in Patients with Philadelphia Chromosome-Positive Advanced Myeloid Leukemias\|url=https://pubmed.ncbi.nlm.nih.gov/32289808\|journal=Acta Haematologica\|volume=143\|issue=6\|pages=567–573\|doi=10.1159/000506346\|issn=1421-9662\|pmc=7839068\|pmid=32289808}}</ref>.		'''Therapeutics:''' There is currently no standardized treatment approach for BCR-ABL1 positive AML. Therapy with TKI alone does not produce sustained responses in BCR-ABL1 positive AML<ref name=":3" />. This may be due to a very rapid clonal evolution, resulting in resistance in a much higher proportion of patients and in a significantly shorter time than in CML<ref name=":2" />.Venetoclax and TKI combination regimens have shown good response in some studies<ref>{{Cite journal\|last=Maiti\|first=Abhishek\|last2=Franquiz\|first2=Miguel J.\|last3=Ravandi\|first3=Farhad\|last4=Cortes\|first4=Jorge E.\|last5=Jabbour\|first5=Elias J.\|last6=Sasaki\|first6=Koji\|last7=Marx\|first7=Kayleigh\|last8=Daver\|first8=Naval G.\|last9=Kadia\|first9=Tapan M.\|date=2020\|title=Venetoclax and BCR-ABL Tyrosine Kinase Inhibitor Combinations: Outcome in Patients with Philadelphia Chromosome-Positive Advanced Myeloid Leukemias\|url=https://pubmed.ncbi.nlm.nih.gov/32289808\|journal=Acta Haematologica\|volume=143\|issue=6\|pages=567–573\|doi=10.1159/000506346\|issn=1421-9662\|pmc=7839068\|pmid=32289808}}</ref>.
	\|Yes (WHO, NCCN)		\|Yes (WHO, NCCN)
	\|The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context<ref>{{Cite journal\|last=Cross\|first=Nicholas C. P.\|last2=Ernst\|first2=Thomas\|last3=Branford\|first3=Susan\|last4=Cayuela\|first4=Jean-Michel\|last5=Deininger\|first5=Michael\|last6=Fabarius\|first6=Alice\|last7=Kim\|first7=Dennis Dong Hwan\|last8=Machova Polakova\|first8=Katerina\|last9=Radich\|first9=Jerald P.\|date=2023-11\|title=European LeukemiaNet laboratory recommendations for the diagnosis and management of chronic myeloid leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/37794101\|journal=Leukemia\|volume=37\|issue=11\|pages=2150–2167\|doi=10.1038/s41375-023-02048-y\|issn=1476-5551\|pmc=10624636\|pmid=37794101}}</ref><ref>{{Cite journal\|last=Sawyers\|first=C. L.\|date=1999-04-29\|title=Chronic myeloid leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/10219069\|journal=The New England Journal of Medicine\|volume=340\|issue=17\|pages=1330–1340\|doi=10.1056/NEJM199904293401706\|issn=0028-4793\|pmid=10219069}}</ref>. This fusion is responsive to targeted therapy such as Imatinib (Gleevec)<ref>{{Cite journal\|last=Cortes\|first=Jorge E.\|last2=Talpaz\|first2=Moshe\|last3=Giles\|first3=Francis\|last4=O'Brien\|first4=Susan\|last5=Rios\|first5=Mary Beth\|last6=Shan\|first6=Jianqin\|last7=Garcia-Manero\|first7=Guillermo\|last8=Faderl\|first8=Stefan\|last9=Thomas\|first9=Deborah A.\|date=2003-05-15\|title=Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy\|url=https://pubmed.ncbi.nlm.nih.gov/12560227\|journal=Blood\|volume=101\|issue=10\|pages=3794–3800\|doi=10.1182/blood-2002-09-2790\|issn=0006-4971\|pmid=12560227}}</ref>.		\|The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context<ref>{{Cite journal\|last=Cross\|first=Nicholas C. P.\|last2=Ernst\|first2=Thomas\|last3=Branford\|first3=Susan\|last4=Cayuela\|first4=Jean-Michel\|last5=Deininger\|first5=Michael\|last6=Fabarius\|first6=Alice\|last7=Kim\|first7=Dennis Dong Hwan\|last8=Machova Polakova\|first8=Katerina\|last9=Radich\|first9=Jerald P.\|date=2023-11\|title=European LeukemiaNet laboratory recommendations for the diagnosis and management of chronic myeloid leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/37794101\|journal=Leukemia\|volume=37\|issue=11\|pages=2150–2167\|doi=10.1038/s41375-023-02048-y\|issn=1476-5551\|pmc=10624636\|pmid=37794101}}</ref><ref>{{Cite journal\|last=Sawyers\|first=C. L.\|date=1999-04-29\|title=Chronic myeloid leukemia\|url=https://pubmed.ncbi.nlm.nih.gov/10219069\|journal=The New England Journal of Medicine\|volume=340\|issue=17\|pages=1330–1340\|doi=10.1056/NEJM199904293401706\|issn=0028-4793\|pmid=10219069}}</ref>. The prevalence of BCR"" ABL1 in CML is common ~90-95%<ref>{{Cite journal\|last=Sharma\|first=Diwakar\|last2=Wilson\|first2=Christine\|last3=Kumar\|first3=Sachin\|last4=Ghose\|first4=Sampa\|last5=Sahoo\|first5=Ranjit\|last6=Sharawat\|first6=Surender K.\|date=2024-08-01\|title=Does presence of complex translocations involving BCR::ABL1 in chronic myeloid leukemia affect the response rate to tyrosine kinase inhibitors? A systematic review of the literature\|url=https://linkinghub.elsevier.com/retrieve/pii/S1092913424000406\|journal=Annals of Diagnostic Pathology\|volume=71\|pages=152303\|doi=10.1016/j.anndiagpath.2024.152303\|issn=1092-9134}}</ref>. This fusion is responsive to targeted therapy such as Imatinib (Gleevec)<ref>{{Cite journal\|last=Cortes\|first=Jorge E.\|last2=Talpaz\|first2=Moshe\|last3=Giles\|first3=Francis\|last4=O'Brien\|first4=Susan\|last5=Rios\|first5=Mary Beth\|last6=Shan\|first6=Jianqin\|last7=Garcia-Manero\|first7=Guillermo\|last8=Faderl\|first8=Stefan\|last9=Thomas\|first9=Deborah A.\|date=2003-05-15\|title=Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy\|url=https://pubmed.ncbi.nlm.nih.gov/12560227\|journal=Blood\|volume=101\|issue=10\|pages=3794–3800\|doi=10.1182/blood-2002-09-2790\|issn=0006-4971\|pmid=12560227}}</ref>.


Line 89:		Line 89:


	There is a single case report of a patient achieving molecular remission with dasatinib and chemotherapy<ref>{{Cite journal\|last=Shao\|first=Xiaoyan\|last2=Chen\|first2=Dangui\|last3=Xu\|first3=Peipei\|last4=Peng\|first4=Miaoxin\|last5=Guan\|first5=Chaoyang\|last6=Xie\|first6=Pinhao\|last7=Yuan\|first7=Cuiying\|last8=Chen\|first8=Bing\|date=2018-11\|title=Primary Philadelphia chromosome positive acute myeloid leukemia: A case report\|url=https://pubmed.ncbi.nlm.nih.gov/30383645\|journal=Medicine\|volume=97\|issue=44\|pages=e12949\|doi=10.1097/MD.0000000000012949\|issn=1536-5964\|pmc=6221582\|pmid=30383645}}</ref>.		The prevalence of BCR::ABL1 in AML is rare (~0.5 - 3%)<ref name=":5" />, per 5th WHO guideline the prevalence is <0.5%<ref>Tumours, 5th edition, IARC Press:Lyon, 2024. Online at: WHO Classification of Tumours.</ref>.

			There is a single case report of an AML patient with BCR::ABL1 achieving molecular remission with dasatinib and chemotherapy<ref>{{Cite journal\|last=Shao\|first=Xiaoyan\|last2=Chen\|first2=Dangui\|last3=Xu\|first3=Peipei\|last4=Peng\|first4=Miaoxin\|last5=Guan\|first5=Chaoyang\|last6=Xie\|first6=Pinhao\|last7=Yuan\|first7=Cuiying\|last8=Chen\|first8=Bing\|date=2018-11\|title=Primary Philadelphia chromosome positive acute myeloid leukemia: A case report\|url=https://pubmed.ncbi.nlm.nih.gov/30383645\|journal=Medicine\|volume=97\|issue=44\|pages=e12949\|doi=10.1097/MD.0000000000012949\|issn=1536-5964\|pmc=6221582\|pmid=30383645}}</ref>.


Line 162:		Line 164:
	\|-		\|-
	\|AML-myelodysplasia-related (AML-MR) cytogenetic aberrations:		\|AML-myelodysplasia-related (AML-MR) cytogenetic aberrations:
	• del(5q), t(5q)~~<ref name=":12" />~~		• del(5q), t(5q)

	• inv(3)(q21q26)~~<ref name=":12" />~~		• inv(3)(q21q26)

	• ‐7, del(7q)<ref>{{Cite journal\|last=Tirado\|first=Carlos A.\|last2=Valdez\|first2=Federico\|last3=Klesse\|first3=Laura\|last4=Karandikar\|first4=Nitin J.\|last5=Uddin\|first5=Naseem\|last6=Arbini\|first6=Arnaldo\|last7=Fustino\|first7=Nicholas\|last8=Collins\|first8=Robert\|last9=Patel\|first9=Sangeeta\|date=2010-07\|title=Acute myeloid leukemia with inv(16) with CBFB–MYH11, 3′CBFB deletion, variant t(9;22) with BCR–ABL1, and del(7)(q22q32) in a pediatric patient: case report and literature review\|url=https://doi.org/10.1016/j.cancergencyto.2010.03.001\|journal=Cancer Genetics and Cytogenetics\|volume=200\|issue=1\|pages=54–59\|doi=10.1016/j.cancergencyto.2010.03.001\|issn=0165-4608}}</ref>		• ‐7, del(7q)

	\|Unknown		\|Unknown
Line 174:		Line 176:
	\|The rarity of Philadelphia-positive subclones in AML patients with specific genetic lesions requires more cases for conclusive prognosis and therapeutic insights<ref name=":12" />.		\|The rarity of Philadelphia-positive subclones in AML patients with specific genetic lesions requires more cases for conclusive prognosis and therapeutic insights<ref name=":12" />.

	In AML, BCR-ABL appears to interact with specific aberrations like inv(16) and myelodysplasia-related cytogenetic changes, but the mechanisms of disease initiation and cooperation remain unclear<ref name=":2" />.		In AML, BCR-ABL appears to interact with specific aberrations like inv(16) and myelodysplasia-related cytogenetic changes, like del(5q), t(5q)<ref name=":12" />, inv(3)(q21q26)<ref name=":12" />, ‐7, del(7q)<ref>{{Cite journal\|last=Tirado\|first=Carlos A.\|last2=Valdez\|first2=Federico\|last3=Klesse\|first3=Laura\|last4=Karandikar\|first4=Nitin J.\|last5=Uddin\|first5=Naseem\|last6=Arbini\|first6=Arnaldo\|last7=Fustino\|first7=Nicholas\|last8=Collins\|first8=Robert\|last9=Patel\|first9=Sangeeta\|date=2010-07\|title=Acute myeloid leukemia with inv(16) with CBFB–MYH11, 3′CBFB deletion, variant t(9;22) with BCR–ABL1, and del(7)(q22q32) in a pediatric patient: case report and literature review\|url=https://doi.org/10.1016/j.cancergencyto.2010.03.001\|journal=Cancer Genetics and Cytogenetics\|volume=200\|issue=1\|pages=54–59\|doi=10.1016/j.cancergencyto.2010.03.001\|issn=0165-4608}}</ref>, but the mechanisms of disease initiation and cooperation remain unclear<ref name=":2" />.
	\|}<br />		\|}<br />
	==Gene Mutations (SNV/INDEL)==		==Gene Mutations (SNV/INDEL)==
Line 195:		Line 197:
	\|Common (BCR-ABL1 AML)		\|Common (BCR-ABL1 AML)
	\|D,P		\|D,P
	\|~~Yes (NCCN, WHO)~~		\|No
	\|AML with ''RUNX1'' mutation is associated with a poorer prognosis<ref name=":6" />. ''RUNX1'' was the most commonly mutated gene, altered in eight of 21 BCR-ABL1 AML cases (38%)<ref name=":13" />.		\|AML with ''RUNX1'' mutation is associated with a poorer prognosis<ref name=":6" />. ''RUNX1'' was the most commonly mutated gene, altered in eight of 21 BCR-ABL1 AML cases (38%)<ref name=":13" />.
	Mutations in five genes (''BCOR, BCORL1, SF3B1, SRSF2,'' and ''STAG2''), along with ''ASXL1'' and ''RUNX1'' mutations, are linked to the proposed high-risk AML chromatin-spliceosome group<ref name=":13" />.		Mutations in five genes (''BCOR, BCORL1, SF3B1, SRSF2,'' and ''STAG2''), along with ''ASXL1'' and ''RUNX1'' mutations, are linked to the proposed high-risk AML chromatin-spliceosome group<ref name=":13" />.