Acute megakaryoblastic leukaemia
Haematolymphoid Tumours (5th ed.)
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editHAEM5 Conversion NotesThis page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Acute Megakaryoblastic Leukemia (AMKL).
(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples). Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)
Primary Author(s)*
Fei Yang, MD, FACMG
Oregon Health & Science University, Portland, OR
Cancer Category / Type
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 HAEM4:Acute Myeloid Leukemia (AML), Not Otherwise Specified[1][2]. 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 HAEM5:Myeloid proliferations associated with Down syndrome[2].
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[2].
Synonyms / Terminology
French-American-British (FAB) classification M7[2].
Epidemiology / Prevalence
AMKL comprises between 4% and 15% of newly diagnosed pediatric acute myeloid leukemia patients[3].
Clinical Features
Put your text here and fill in the table (Instruction: Can include references in the table)
| Signs and Symptoms | EXAMPLE Asymptomatic (incidental finding on complete blood counts)
EXAMPLE B-symptoms (weight loss, fever, night sweats) EXAMPLE Fatigue EXAMPLE Lymphadenopathy (uncommon) |
| Laboratory Findings | EXAMPLE Cytopenias
EXAMPLE Lymphocytosis (low level) |
editv4:Clinical FeaturesThe content below was from the old template. Please incorporate above.
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
| Finding | Marker |
|---|---|
| Positive (universal) | EXAMPLE CD1 |
| Positive (subset) | EXAMPLE CD2 |
| Negative (universal) | EXAMPLE CD3 |
| Negative (subset) | EXAMPLE CD4 |
Chromosomal Rearrangements (Gene Fusions)
Put your text here and fill in the table
| Chromosomal Rearrangement | Genes in Fusion (5’ or 3’ Segments) | Pathogenic Derivative | Prevalence | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|---|---|---|
| EXAMPLE t(9;22)(q34;q11.2) | EXAMPLE 3'ABL1 / 5'BCR | EXAMPLE der(22) | EXAMPLE 20% (COSMIC)
EXAMPLE 30% (add reference) |
Yes | No | Yes | EXAMPLE
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). |
editv4:Chromosomal Rearrangements (Gene Fusions)The content below was from the old template. Please incorporate above.None.
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%
editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).Please incorporate this section into the relevant tables found in:
- Chromosomal Rearrangements (Gene Fusions)
- Individual Region Genomic Gain/Loss/LOH
- Characteristic Chromosomal Patterns
- Gene Mutations (SNV/INDEL)
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[2].
Prognosis
- 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[2][5].
Individual Region Genomic Gain / Loss / LOH
Put your text here and fill in the table (Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.)
| Chr # | Gain / Loss / Amp / LOH | Minimal Region Genomic Coordinates [Genome Build] | Minimal Region Cytoband | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|---|---|---|
| EXAMPLE
7 |
EXAMPLE Loss | EXAMPLE
chr7:1- 159,335,973 [hg38] |
EXAMPLE
chr7 |
Yes | Yes | No | EXAMPLE
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference). |
| EXAMPLE
8 |
EXAMPLE Gain | EXAMPLE
chr8:1-145,138,636 [hg38] |
EXAMPLE
chr8 |
No | No | No | EXAMPLE
Common recurrent secondary finding for t(8;21) (add reference). |
editv4:Genomic Gain/Loss/LOHThe content below was from the old template. Please incorporate above.None
Chromosome Number Gain/Loss/Amp/LOH Region EXAMPLE 8 EXAMPLE Gain EXAMPLE chr8:0-1000000 EXAMPLE 7 EXAMPLE Loss EXAMPLE chr7:0-1000000
Characteristic Chromosomal Patterns
Put your text here (EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis)
| Chromosomal Pattern | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|
| EXAMPLE
Co-deletion of 1p and 18q |
Yes | No | No | EXAMPLE:
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). |
editv4:Characteristic Chromosomal Aberrations / PatternsThe content below was from the old template. Please incorporate above.
- No unique chromosomal abnormality is associated with AMKL.
- Isochromosome 12p is often observed in young males with mediatinal germ tumors and AMKL[6].
Gene Mutations (SNV / INDEL)
Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.)
| Gene; Genetic Alteration | Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other) | Prevalence (COSMIC / TCGA / Other) | Concomitant Mutations | Mutually Exclusive Mutations | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|---|---|---|---|
| EXAMPLE: TP53; Variable LOF mutations
EXAMPLE: EGFR; Exon 20 mutations EXAMPLE: BRAF; Activating mutations |
EXAMPLE: TSG | EXAMPLE: 20% (COSMIC)
EXAMPLE: 30% (add Reference) |
EXAMPLE: IDH1 R123H | EXAMPLE: EGFR amplification | EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference).
|
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
editv4:Gene Mutations (SNV/INDEL)The content below was from the old template. Please incorporate above.None.
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
Type Gene/Region/Other Concomitant Mutations EXAMPLE IDH1 R123H Secondary Mutations EXAMPLE Trisomy 7 Mutually Exclusive EXAMPLE EGFR Amplification
Epigenomic Alterations
None.
Genes and Main Pathways Involved
Put your text here and fill in the table (Instructions: Can include references in the table.)
| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| EXAMPLE: BRAF and MAP2K1; Activating mutations | EXAMPLE: MAPK signaling | EXAMPLE: Increased cell growth and proliferation |
| EXAMPLE: CDKN2A; Inactivating mutations | EXAMPLE: Cell cycle regulation | EXAMPLE: Unregulated cell division |
| EXAMPLE: KMT2C and ARID1A; Inactivating mutations | EXAMPLE: Histone modification, chromatin remodeling | EXAMPLE: Abnormal gene expression program |
editv4:Genes and Main Pathways InvolvedThe content below was from the old template. Please incorporate above.None.
Genetic Diagnostic Testing Methods
- Conventional chromosome analysis
- FISH myeloid panel
Familial Forms
Put your text here (Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.)
Additional Information
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Links
Put your links here
References
(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference.)
- ↑ 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.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Arber, Daniel A.; et al. (2016). "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia". Blood. 127 (20): 2391–2405. doi:10.1182/blood-2016-03-643544. ISSN 1528-0020. PMID 27069254.
- ↑ Gruber, Tanja A.; et al. (2015). "The biology of pediatric acute megakaryoblastic leukemia". Blood. 126 (8): 943–949. doi:10.1182/blood-2015-05-567859. ISSN 1528-0020. PMC 4551356. PMID 26186939.
- ↑ Nichols, C. R.; et al. (1990). "Hematologic neoplasia associated with primary mediastinal germ-cell tumors". The New England Journal of Medicine. 322 (20): 1425–1429. doi:10.1056/NEJM199005173222004. ISSN 0028-4793. PMID 2158625.
- ↑ Oki, Yasuhiro; et al. (2006). "Adult acute megakaryocytic leukemia: an analysis of 37 patients treated at M.D. Anderson Cancer Center". Blood. 107 (3): 880–884. doi:10.1182/blood-2005-06-2450. ISSN 0006-4971. PMID 16123215.
- ↑ Orazi, A.; et al. (1993). "Hematopoietic precursor cells within the yolk sac tumor component are the source of secondary hematopoietic malignancies in patients with mediastinal germ cell tumors". Cancer. 71 (12): 3873–3881. doi:10.1002/1097-0142(19930615)71:123.0.co;2-1. ISSN 0008-543X. PMID 8389653.
Notes
*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. *Citation of this Page: “Acute megakaryoblastic leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 12/13/2023, https://ccga.io/index.php/HAEM5:Acute_megakaryoblastic_leukaemia.