Acute Megakaryoblastic Leukemia (AMKL)
Fei Yang, MD, FACMG
Oregon Health & Science University, Portland, OR
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. 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.
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.
Synonyms / Terminology
French-American-British (FAB) classification M7.
Epidemiology / Prevalence
AMKL comprises between 4% and 15% of newly diagnosed pediatric acute myeloid leukemia patients.
- Common manifestations include cytopenias (often thrombocytopenia).
- An association between acute megakaryoblastic leukemia and mediastrinal germ cell tumors has been described.
Sites of Involvement
- 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.
- 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.
- 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
|Positive (universal)||EXAMPLE CD1|
|Positive (subset)||EXAMPLE CD2|
|Negative (universal)||EXAMPLE CD3|
|Negative (subset)||EXAMPLE CD4|
Chromosomal Rearrangements (Gene Fusions)
|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.
|EXAMPLE 8||EXAMPLE Gain||EXAMPLE chr8:0-1000000|
|EXAMPLE 7||EXAMPLE Loss||EXAMPLE chr7:0-1000000|
Gene Mutations (SNV/INDEL)
|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%|
|Concomitant Mutations||EXAMPLE IDH1 R123H|
|Secondary Mutations||EXAMPLE Trisomy 7|
|Mutually Exclusive||EXAMPLE EGFR Amplification|
Genes and Main Pathways Involved
Diagnostic Testing Methods
- Conventional chromosome analysis
- FISH myeloid panel
Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)
- 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.
- 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.
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- ↑ 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.
- ↑ 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.
- ↑ 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.
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