Acute Megakaryoblastic Leukemia (AMKL)

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Primary Author(s)*

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

Cancer Category/Type

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[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 Myeloid Leukemia 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 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[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

  • Common manifestations include cytopenias (often thrombocytopenia)[2].
  • An association between acute megakaryoblastic leukemia and mediastrinal germ cell tumors has been described[4].

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.



  • 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)


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[5].

Genomic Gain/Loss/LOH


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)


Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other)

Other Mutations

Type Gene/Region/Other
Concomitant Mutations EXAMPLE IDH1 R123H
Secondary Mutations EXAMPLE Trisomy 7
Mutually Exclusive EXAMPLE EGFR Amplification

Epigenomics (Methylation)


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[2].


Familial Forms

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Other Information

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  1. 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. 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.
  3. 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.
  4. 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.
  5. 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);2-1. ISSN 0008-543X. PMID 8389653.
  6. 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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