Acute megakaryoblastic leukemia
Acute megakaryoblastic leukemia (AMKL) is a cytological subgroup of acute myeloid leukemia (AML) that harbors megakaryocytic lineage markers (eg, CD41, CD42, and CD61).
AMKL occurrence is almost entirely restricted to children (usually < 3 years of age), occurring in only 1% of adult AML cases, often after progression from myelodysplastic syndromes. AMKL represents ∼10% of pediatric AML cases and has been long recognized for its poor prognosis.
Clinically, AMKL diagnosis remains challenging due to marked myelofibrosis and resulting hypocellular bone marrow (BM) aspirates, lack of disease-specific cell surface markers and, until recently, limited molecular markers.
Interestingly, children with Down syndrome (DS; trisomy 21) are at increased risk of developing AMKL, but they have better survival than non-DS patients, suggesting 2 distinct types of disease.
Oncogenic gene fusions are recurrent, mutually exclusive mutations found in more than 70% of non-DS pediatric AMKL.
- CBFA2T3-GLIS2 (∼18%);
- MLL rearrangements (MLLr; ∼17%);
- HOX rearrangements (HOXr; ∼15%);
- NUP98-KDM5A (N5A; ∼11%);
- RBM15-MKL1 (∼10%).
Patients presenting with AMKL assigned to the CBFA2T3-GLIS2, MLLr, and N5A molecular subsets typically experience poor outcomes.
Cardin S, Bilodeau M, Roussy M, et al. Human models of NUP98-KDM5A megakaryocytic leukemia in mice contribute to uncovering new biomarkers and therapeutic vulnerabilities. Blood Adv. 2019;3(21):3307–3321. doi:10.1182/bloodadvances.2019030981