HAEM4:Acute Megakaryoblastic Leukemia (AMKL) - Revision history

Bailey.Glen at 21:28, 4 December 2023

2023-12-04T21:28:16Z

← Older revision		Revision as of 16:28, 4 December 2023
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	==Definition / Description of Disease==		==Definition / Description of Disease==

	Acute megakaryoblastic leukemia is a myeloid disease defined by ≥20% blasts in the peripheral blood or bone marrow, of which ≥50% are of megakaryocyte lineage. In the 2016 revision to the World Health Organization (WHO) classification system, acute megakaryoblastic leukemia is a distinct entity within the section of [[Acute Myeloid Leukemia (AML), Not Otherwise Specified]]<ref>Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. IARC Press: Lyon, France, p162-164.</ref><ref name=":0">{{Cite journal\|last=Arber\|first=Daniel A.\|last2=Orazi\|first2=Attilio\|last3=Hasserjian\|first3=Robert\|last4=Thiele\|first4=Jürgen\|last5=Borowitz\|first5=Michael J.\|last6=Le Beau\|first6=Michelle M.\|last7=Bloomfield\|first7=Clara D.\|last8=Cazzola\|first8=Mario\|last9=Vardiman\|first9=James W.\|date=2016\|title=The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia\|url=https://www.ncbi.nlm.nih.gov/pubmed/27069254\|journal=Blood\|volume=127\|issue=20\|pages=2391–2405\|doi=10.1182/blood-2016-03-643544\|issn=1528-0020\|pmid=27069254}}</ref>. This entity does not meet the criteria for inclusion in any of the other AML groups (i.e. AML with Recurrent Genetic Abnormalities, AML with Myelodysplasia-Related Changes, or Therapy-Related Myeloid Neoplasms).		Acute megakaryoblastic leukemia is a myeloid disease defined by ≥20% blasts in the peripheral blood or bone marrow, of which ≥50% are of megakaryocyte lineage. In the 2016 revision to the World Health Organization (WHO) classification system, acute megakaryoblastic leukemia is a distinct entity within the section of [[HAEM4:Acute Myeloid Leukemia (AML), Not Otherwise Specified]]<ref>Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. IARC Press: Lyon, France, p162-164.</ref><ref name=":0">{{Cite journal\|last=Arber\|first=Daniel A.\|last2=Orazi\|first2=Attilio\|last3=Hasserjian\|first3=Robert\|last4=Thiele\|first4=Jürgen\|last5=Borowitz\|first5=Michael J.\|last6=Le Beau\|first6=Michelle M.\|last7=Bloomfield\|first7=Clara D.\|last8=Cazzola\|first8=Mario\|last9=Vardiman\|first9=James W.\|date=2016\|title=The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia\|url=https://www.ncbi.nlm.nih.gov/pubmed/27069254\|journal=Blood\|volume=127\|issue=20\|pages=2391–2405\|doi=10.1182/blood-2016-03-643544\|issn=1528-0020\|pmid=27069254}}</ref>. This entity does not meet the criteria for inclusion in any of the other AML groups (i.e. AML with Recurrent Genetic Abnormalities, AML with Myelodysplasia-Related Changes, or Therapy-Related Myeloid Neoplasms).

	AMKL in an individual with Down syndrome should be classified as a different entity, specifically [[Myeloid ~~Leukemia Associated~~ with Down ~~Syndrome~~]]<ref name=":0" />.		AMKL in an individual with Down syndrome should be classified as a different entity, specifically [[HAEM5:Myeloid proliferations associated with Down syndrome]]<ref name=":0" />.

	AMKL associated with t(1;22)(p13.3;q13.1), or inv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2) should be classified as a different entity, specifically [[Acute Myeloid Leukemia (AML) with Recurrent Genetic Abnormalities]]: [[Acute ~~Myeloid Leukemia (AML) Megakaryoblastic~~ with ~~t(1;22)(p13.3;q13.1);~~RBM15~~-MKL1~~]] or [[Acute ~~Myeloid Leukemia (AML)~~ with ~~inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2);GATA2,~~ MECOM]]<ref name=":0" />.		AMKL associated with t(1;22)(p13.3;q13.1), or inv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2) should be classified as a different entity, specifically [[HAEM4:Acute Myeloid Leukemia (AML) with Recurrent Genetic Abnormalities]]: [[HAEM5:Acute myeloid leukaemia with RBM15::MRTFA fusion]] or [[HAEM5:Acute myeloid leukaemia with MECOM rearrangement]]<ref name=":0" />.

	==Synonyms / Terminology==		==Synonyms / Terminology==
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	Prognosis		Prognosis

	*The prognosis of AMKL is usually poorer than that of other AML types, [[Acute ~~Myeloid Leukemia (AML) Megakaryoblastic~~ with ~~t(1;22)(p13.3;q13.1);~~RBM15~~-MKL1~~]], and [[ Myeloid ~~Leukemia Associated~~ with Down ~~Syndrome~~]]<ref name=":0" /><ref>{{Cite journal\|last=Oki\|first=Yasuhiro\|last2=Kantarjian\|first2=Hagop M.\|last3=Zhou\|first3=Xian\|last4=Cortes\|first4=Jorge\|last5=Faderl\|first5=Stefan\|last6=Verstovsek\|first6=Srdan\|last7=O'Brien\|first7=Susan\|last8=Koller\|first8=Charles\|last9=Beran\|first9=Miloslav\|date=2006\|title=Adult acute megakaryocytic leukemia: an analysis of 37 patients treated at M.D. Anderson Cancer Center\|url=https://www.ncbi.nlm.nih.gov/pubmed/16123215\|journal=Blood\|volume=107\|issue=3\|pages=880–884\|doi=10.1182/blood-2005-06-2450\|issn=0006-4971\|pmid=16123215}}</ref>.		*The prognosis of AMKL is usually poorer than that of other AML types, [[HAEM5:Acute myeloid leukaemia with RBM15::MRTFA fusion]], and [[HAEM5:Myeloid proliferations associated with Down syndrome]]<ref name=":0" /><ref>{{Cite journal\|last=Oki\|first=Yasuhiro\|last2=Kantarjian\|first2=Hagop M.\|last3=Zhou\|first3=Xian\|last4=Cortes\|first4=Jorge\|last5=Faderl\|first5=Stefan\|last6=Verstovsek\|first6=Srdan\|last7=O'Brien\|first7=Susan\|last8=Koller\|first8=Charles\|last9=Beran\|first9=Miloslav\|date=2006\|title=Adult acute megakaryocytic leukemia: an analysis of 37 patients treated at M.D. Anderson Cancer Center\|url=https://www.ncbi.nlm.nih.gov/pubmed/16123215\|journal=Blood\|volume=107\|issue=3\|pages=880–884\|doi=10.1182/blood-2005-06-2450\|issn=0006-4971\|pmid=16123215}}</ref>.

	==Familial Forms==		==Familial Forms==

Bailey.Glen at 18:46, 3 November 2023

2023-11-03T18:46:57Z

← Older revision		Revision as of 13:46, 3 November 2023
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			{{DISPLAYTITLE:Acute Megakaryoblastic Leukemia (AMKL)}}


			<blockquote class='blockedit'>{{Box-round\|title=PREVIOUS EDITION\|This page from the 4th edition of Haematolymphoid Tumours is being updated. See 5th edition [[HAEM5:Table_of_Contents\|Table of Contents]].
			}}</blockquote>
	==Primary Author(s)*==		==Primary Author(s)*==

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	==Notes==		==Notes==
	<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.		<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.
			[[Category:HAEM4]] [[Category:DISEASE]]

	[[Category:~~Recently Added Pages~~]]

Bailey.Glen: Created page with "==Primary Author(s)*== Fei Yang, MD, FACMG
Oregon Health & Science University, Portland, OR TOC ==Cancer Category/Type== Acute Myeloid Leukemia ==Cancer..."

2023-11-03T18:06:21Z

Created page with "==Primary Author(s)*== Fei Yang, MD, FACMG <br> Oregon Health & Science University, Portland, OR __TOC__ ==Cancer Category/Type== Acute Myeloid Leukemia ==Cancer..."

New page

==Primary Author(s)*==

Fei Yang, MD, FACMG
<br>
Oregon Health & Science University, Portland, OR

__TOC__

==Cancer Category/Type==

[[AML|Acute Myeloid Leukemia]]

==Cancer Sub-Classification / Subtype==

Acute Megakaryoblastic Leukemia

==Definition / Description of Disease==

Acute megakaryoblastic leukemia is a myeloid disease defined by ≥20% blasts in the peripheral blood or bone marrow, of which ≥50% are of megakaryocyte lineage. In the 2016 revision to the World Health Organization (WHO) classification system, acute megakaryoblastic leukemia is a distinct entity within the section of [[Acute Myeloid Leukemia (AML), Not Otherwise Specified]]<ref>Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. IARC Press: Lyon, France, p162-164.</ref><ref name=":0">{{Cite journal|last=Arber|first=Daniel A.|last2=Orazi|first2=Attilio|last3=Hasserjian|first3=Robert|last4=Thiele|first4=Jürgen|last5=Borowitz|first5=Michael J.|last6=Le Beau|first6=Michelle M.|last7=Bloomfield|first7=Clara D.|last8=Cazzola|first8=Mario|last9=Vardiman|first9=James W.|date=2016|title=The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/27069254|journal=Blood|volume=127|issue=20|pages=2391–2405|doi=10.1182/blood-2016-03-643544|issn=1528-0020|pmid=27069254}}</ref>. This entity does not meet the criteria for inclusion in any of the other AML groups (i.e. AML with Recurrent Genetic Abnormalities, AML with Myelodysplasia-Related Changes, or Therapy-Related Myeloid Neoplasms).

AMKL in an individual with Down syndrome should be classified as a different entity, specifically [[Myeloid Leukemia Associated with Down Syndrome]]<ref name=":0" />.

AMKL associated with t(1;22)(p13.3;q13.1), or inv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2) should be classified as a different entity, specifically [[Acute Myeloid Leukemia (AML) with Recurrent Genetic Abnormalities]]: [[Acute Myeloid Leukemia (AML) Megakaryoblastic with t(1;22)(p13.3;q13.1);RBM15-MKL1]] or [[Acute Myeloid Leukemia (AML) with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2);GATA2, MECOM]]<ref name=":0" />.

==Synonyms / Terminology==

French-American-British (FAB) classification M7<ref name=":0" />.

==Epidemiology / Prevalence==

AMKL comprises between 4% and 15% of newly diagnosed pediatric acute myeloid leukemia patients<ref>{{Cite journal|last=Gruber|first=Tanja A.|last2=Downing|first2=James R.|date=2015|title=The biology of pediatric acute megakaryoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/26186939|journal=Blood|volume=126|issue=8|pages=943–949|doi=10.1182/blood-2015-05-567859|issn=1528-0020|pmc=4551356|pmid=26186939}}</ref>.

==Clinical Features==

*Common manifestations include cytopenias (often thrombocytopenia)<ref name=":0" />.
*An association between acute megakaryoblastic leukemia and mediastrinal germ cell tumors has been described<ref>{{Cite journal|last=Nichols|first=C. R.|last2=Roth|first2=B. J.|last3=Heerema|first3=N.|last4=Griep|first4=J.|last5=Tricot|first5=G.|date=1990|title=Hematologic neoplasia associated with primary mediastinal germ-cell tumors|url=https://www.ncbi.nlm.nih.gov/pubmed/2158625|journal=The New England Journal of Medicine|volume=322|issue=20|pages=1425–1429|doi=10.1056/NEJM199005173222004|issn=0028-4793|pmid=2158625}}</ref>.

==Sites of Involvement==

Bone marrow.

==Morphologic Features==

*Megakaryoblasts are usually medium-sized to large cells with basophilic cytoplasm and a high nuclear-cytoplasmic ratio.
*Nuclei are round, slightly irregular or indented with finely reticular chromatin and 1 - 3 nucleoli.
*Bone marrow myelofibrosis is common.

==Immunophenotype==

Cytochemistry

*Megakaryoblasts are typically negative for myeloperoxidase (MPO) and stain negatively with Sudan black B.
*Variable reactivity to periodic acid-Schiff (PAS) staining from negative to focal or strongly positive.

Immunophenotype including:

*One or more of the platelet glycoproteins: CD41, CD61, and CD42b
*Myeloid-associated markers may be positive: CD13, CD33
*CD34, CD45, and HLA-DR are often negative, especially in children

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||EXAMPLE CD1
|-
|Positive (subset)||EXAMPLE CD2
|-
|Negative (universal)||EXAMPLE CD3
|-
|Negative (subset)||EXAMPLE CD4
|}

==Chromosomal Rearrangements (Gene Fusions)==

None.

{| class="wikitable sortable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 5%
|-
|EXAMPLE t(8;21)(q22;q22)||EXAMPLE 5'RUNX1 / 3'RUNXT1||EXAMPLE der(8)||EXAMPLE 5%
|}

==Characteristic Chromosomal Aberrations / Patterns==

*No unique chromosomal abnormality is associated with AMKL.

*Isochromosome 12p is often observed in young males with mediatinal germ tumors and AMKL<ref>{{Cite journal|last=Orazi|first=A.|last2=Neiman|first2=R. S.|last3=Ulbright|first3=T. M.|last4=Heerema|first4=N. A.|last5=John|first5=K.|last6=Nichols|first6=C. R.|date=1993|title=Hematopoietic precursor cells within the yolk sac tumor component are the source of secondary hematopoietic malignancies in patients with mediastinal germ cell tumors|url=https://www.ncbi.nlm.nih.gov/pubmed/8389653|journal=Cancer|volume=71|issue=12|pages=3873–3881|doi=10.1002/1097-0142(19930615)71:123.0.co;2-1|issn=0008-543X|pmid=8389653}}</ref>.

==Genomic Gain/Loss/LOH==

None

{| class="wikitable sortable"
|-
!Chromosome Number!!Gain/Loss/Amp/LOH!!Region
|-
|EXAMPLE 8||EXAMPLE Gain||EXAMPLE chr8:0-1000000
|-
|EXAMPLE 7||EXAMPLE Loss||EXAMPLE chr7:0-1000000
|}

==Gene Mutations (SNV/INDEL)==

None.

{| class="wikitable sortable"
|-
!Gene!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)
|-
|EXAMPLE TP53||EXAMPLE R273H||EXAMPLE Tumor Suppressor||EXAMPLE LOF||EXAMPLE 20%
|}

===Other Mutations===
{| class="wikitable sortable"
|-
!Type!!Gene/Region/Other
|-
|Concomitant Mutations||EXAMPLE IDH1 R123H
|-
|Secondary Mutations||EXAMPLE Trisomy 7
|-
|Mutually Exclusive||EXAMPLE EGFR Amplification
|}

==Epigenomics (Methylation)==

None.

==Genes and Main Pathways Involved==

None.

==Diagnostic Testing Methods==

*Conventional chromosome analysis

*FISH myeloid panel

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==

Diagnosis

*The main differential diagnoses of acute megakaryoblastic leukemia include: AML with minimal differentiation, AML-MRC, acute panmeylosis with myelofibrosis, lymphoblastic leukemia, pure erythroid leukemia, blastic transformation of chronic myeloid leukemia, and the blast phase of any other myeloproliferative neoplasm<ref name=":0" />.

Prognosis

*The prognosis of AMKL is usually poorer than that of other AML types, [[Acute Myeloid Leukemia (AML) Megakaryoblastic with t(1;22)(p13.3;q13.1);RBM15-MKL1]], and [[ Myeloid Leukemia Associated with Down Syndrome]]<ref name=":0" /><ref>{{Cite journal|last=Oki|first=Yasuhiro|last2=Kantarjian|first2=Hagop M.|last3=Zhou|first3=Xian|last4=Cortes|first4=Jorge|last5=Faderl|first5=Stefan|last6=Verstovsek|first6=Srdan|last7=O'Brien|first7=Susan|last8=Koller|first8=Charles|last9=Beran|first9=Miloslav|date=2006|title=Adult acute megakaryocytic leukemia: an analysis of 37 patients treated at M.D. Anderson Cancer Center|url=https://www.ncbi.nlm.nih.gov/pubmed/16123215|journal=Blood|volume=107|issue=3|pages=880–884|doi=10.1182/blood-2005-06-2450|issn=0006-4971|pmid=16123215}}</ref>.

==Familial Forms==

Put your text here

==Other Information==

Put your text here

==Links==

Put your links here

==References==
<references />

==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.

[[Category:Recently Added Pages]]

HAEM4:Acute Megakaryoblastic Leukemia (AMKL) - Revision history

Bailey.Glen at 21:28, 4 December 2023

Bailey.Glen at 18:46, 3 November 2023

Bailey.Glen: Created page with "==Primary Author(s)*== Fei Yang, MD, FACMG Oregon Health & Science University, Portland, OR __TOC__ ==Cancer Category/Type== Acute Myeloid Leukemia ==Cancer..."

Bailey.Glen: Created page with "==Primary Author(s)*== Fei Yang, MD, FACMG
Oregon Health & Science University, Portland, OR TOC ==Cancer Category/Type== Acute Myeloid Leukemia ==Cancer..."