HAEM5:Acute myeloid leukaemia with RUNX1::RUNX1T1 fusion: Difference between revisions
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<blockquote class= | <blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Acute Myeloid Leukemia (AML) with t(8;21)(q22;q22.1); RUNX1-RUNX1T1]]. | ||
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|Acute myeloid leukaemia with RUNX1::RUNX1T1 fusion | |Acute myeloid leukaemia with RUNX1::RUNX1T1 fusion | ||
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==WHO Essential and Desirable Genetic Diagnostic Criteria== | ==WHO Essential and Desirable Genetic Diagnostic Criteria== | ||
<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span> | <span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span> | ||
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|} | |}[[File:T_8_21_q22_q22.png|frame|center| Karyogram showing t(8;21)(q22;q22) translocation. Jennifer | ||
Otani, Beth Israel Deaconess Medical Center, Boston, MA]] | |||
[[File:t(8;21)(q22;q22).png|frame|center| t(8;21)(q22;q22)]] | |||
[[File:RUNX1_RUNXT1_FISH_Inverted.png|frame|center| FISH RUNX1-RUNX1T1 probe set on metaphase cell with | |||
t(8;21)(q22;q22) translocation. Jennifer Otani, Beth Israel | |||
Deaconess Medical Center, Boston, MA. | |||
]] | |||
<blockquote class= | <blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote> | ||
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
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<blockquote class= | <blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in: | ||
* Chromosomal Rearrangements (Gene Fusions) | * Chromosomal Rearrangements (Gene Fusions) | ||
* Individual Region Genomic Gain/Loss/LOH | * Individual Region Genomic Gain/Loss/LOH | ||
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<blockquote class= | <blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote> | ||
9q22 loss | 9q22 loss | ||
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<blockquote class= | <blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote> | ||
Additional aberrations in >70% of cases with t(8;21); common loss of a sex chromosome or deletion 9q | Additional aberrations in >70% of cases with t(8;21); common loss of a sex chromosome or deletion 9q | ||
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|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content. | |}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content. | ||
<blockquote class= | <blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote> | ||
AML with t(8;21)(q22;q22) has genetic heterogeneity at the molecular level. Several genes have been identified that are frequently mutated in this subset of AML, some of them adversely affecting prognosis. | AML with t(8;21)(q22;q22) has genetic heterogeneity at the molecular level. Several genes have been identified that are frequently mutated in this subset of AML, some of them adversely affecting prognosis. | ||
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<blockquote class= | <blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote> | ||
Genes: | Genes: | ||
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==Additional Information== | ==Additional Information== | ||
This disease is <u>defined/characterized</u> as detailed below: | |||
Acute myeloid leukemia (AML) with t(8;21)(q22;q22) resulting in RUNX1-RUNX1T1 gene fusion defines a subtype of AML with neutrophil lineage maturation. In the 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia, it is in the group of AML with recurrent genetic abnormalities<ref>{{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>. In the older French-American-British (FAB) classification system, t(8;21)(q22;q22) positive AML belonged to the acute myeloblastic leukemia with maturation M2 category and accounted for 10% of cases. t(8;21)(q22;q22) can occasionally be seen in therapy-related AML. In those instances the leukemia is not classified in the group of AML with recurrent genetic abnormalities due to clinical and prognostic differences. AML with t(8;21)(q22;q22) is a core binding leukemia (see Genes and Main Pathways Involved section below)<ref>{{Cite journal|last=Sangle|first=Nikhil A.|last2=Perkins|first2=Sherrie L.|date=2011|title=Core-binding factor acute myeloid leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/22032582|journal=Archives of Pathology & Laboratory Medicine|volume=135|issue=11|pages=1504–1509|doi=10.5858/arpa.2010-0482-RS|issn=1543-2165|pmid=22032582}}</ref>. | |||
*t(8;21)(q22;q22) is a translocation involving the long arms of chromosomes 8 and 21 that defines a distinctive cytogenetic subtype of [[AML|acute myeloid leukemia]]. | |||
*Complex translocations involving chromosomes 8, 21 and a third chromosome occur; the derivative chromosome 8 in the t(8;21)(q22;q22) and the variant t(8;21;var) carries the RUNX1-RUNX1T1 gene rearrangement. | |||
*Cases with cryptic RUNX1-RUNX1T1 gene rearrangement have been reported. | |||
*Note: The RUNX1T1 gene is currently located at 8q21.3. This gene was previously located at 8q22, which explains the discrepancy in the breakpoint given in the name for this WHO-defined disease entity. | |||
The <u>epidemiology/prevalence</u> of this disease is detailed below: | |||
Approximately 1-5% of AML cases have the t(8;21)(q22;q22.1) | |||
*Occurs mainly in younger patients | |||
*Mean age is 30 years | |||
*Most common type of AML in children | |||
The <u>clinical features</u> of this disease are detailed below: | |||
*May present as a myeloid sarcoma and, if so, the bone marrow aspirate blast count may be misleadingly low | |||
*Concurrent systemic mastocytosis has been reported | |||
The <u>sites of involvement</u> of this disease are detailed below: | |||
* Bone marrow | |||
The <u>morphologic features</u> of this disease are detailed below: | |||
*Large blasts with abundant basophilic cytoplasm often with azurophilic granules and perinuclear clearing | |||
*Long sharp Auer rods are frequently observed. | |||
*Promyelocytes, myelocytes and metamyelocytes may have abnormal nuclear segmentation and cytoplasmic staining. | |||
*Normal eosinophil precursors are frequently increased and do not show the nuclear and cytoplasmic abnormalities seen in AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22). | |||
*Cases with t(8;21)(q22;q22.1) and less than 20% blast percentage in the marrow should be classified as AML rather than myelodysplastic syndrome according to the WHO 2017<ref>Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. 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. IARC Press: Lyon, France.</ref>. | |||
[[File:AML_RUNX1_RUNXT1_Path.png|center|frame|Bone marrow aspirate with t(8;21)(q22;q22) | |||
blast with Auer rod (100X). Robert Willim, MD, | |||
Beth Israel Deaconess Medical Center, Boston, MA]]The <u>immunophenotype</u> of this disease is detailed below: | |||
*Blasts express CD34, HLA-DR, MPO, CD13, CD33 (weak), CD15 and/or CD65, co-expression of CD34. Lymphoid markers: CD19, PAX5, sometimes cytoplasmic CD79a | |||
*Occasional weak TdT positivity and/or CD56 expression may have adverse prognosis | |||
==Links== | ==Links== | ||