The Hong Kong Association of Blood Transfusion and Haematology
Acute megakaryoblastic leukaemia with complex variant 1;22 translocation
Dr. Edmond S. K. Ma
Division of Haematology, Department of Pathology, The University of Hong Kong

Case presentation

A 6-month old Indonesian boy presented with fever and hepatosplenomegaly. There was no features of Down's syndrome.

Complete blood counts showed: haemoglobin 8.5 g/dL, white cell count 13 X 109/L, and platelet count 20 X 109/L. Examination of peripheral blood film revealed a leucoerythroblastic blood picture and 9% circulating blasts that were morphologically undifferentiated (Figure 1).

Bone marrow aspirate (Figure 2) and trephine imprint (Figure 3) showed 20% blasts of similar morphology and depression of normal haemopoietic elements. They were cytochemically inert for myeloperoxidase (Figure 4) and sudan black B.

Immunophenotyping of leukaemic blasts in peripheral blood by flow cytometry showed expression of myeloid associated antigen CD33. Platelet markers CD41 and CD61 were also positive. Karyotyping of bone marrow cells showed: 46,XY,t(1;22;6)(p12;q12;q21)[2]/46,XY[8] (Figure 5).

Trephine biopsy showed hypercellular marrow with large clusters of blast cells in a marked fibrotic stroma (Figure 6). The blast cells feature large size, round nucleus, fine chromatin texture and inconspicuous nucleolus. Residual erythroid and myeloid activity were discernible. Eosinophils and eosinophilic myelocytes were prominently seen in the background. Megakaryocytes were reduced. The reticulin pattern was diffusely coarsened.


Acute megakaryoblastic leukaemia (AML-M7), an uncommon disease accounting for 3 - 5% of all AML cases, occurs in both adults and children [1]. Patients usually present with cytopenia. Organomegaly is infrequent except in children with AML-M7 associated with t(1;22) who presents with prominent abdominal masses. An association between AML-M7 and mediastinal germ cell tumours has been observed in young adult males [2].

Megakaryoblasts show heterogeneity in morphological appearance, and may range from those resembling lymphoblasts to large ones with cytoplasmic blebs or pseudopods. Circulating micromegakaryocytes and dysplastic large platelets may be present. Underlying marrow fibrosis is common but not an invariant finding. Trephine biopsy shows poorly differentiated blasts that may be admixed with maturing dysplastic megakaryocytes. The blast population in AML-M7 associated with t(1;22) in infants may show a stromal pattern of marrow infiltration mimicking a metastatic tumour, for example neuroblastoma.

Cytochemical staining for myeloperoxidase and sudan black B are consistently negative. Electron microscopy shows peroxidase activity confined to the nuclear membrane and endoplasmic reticulum with the platelet peroxidase reaction.

Immunophenotyping shows expression of platelet glycoproteins CD41 and CD61, and less frequently CD42b. They are also positive for CD36. There may be aberrant expression of CD7. The myeloid markers CD13 and CD33 may be positive, but CD34, CD45, HLA-DR and anti-MPO are negative.

Cytogenetic associations include:

  1. inv(3)(q21;q26): not specific to AML-M7 and may be seen in other types of AML.

  2. (1;22)(p13;q13): encountered particularly in infants [3] and is associated with a poor prognosis. More recently, this chromosomal rearrangement has been shown to result in the fusion of two novel genes, RNA-binding motif protein-15 (RBM15), an RNA recognition motif-encoding gene with homology to Drosophila spen, and Megakaryoblastic Leukemia-1 (MKL1), a gene encoding an SAP (SAF-A/B, Acinus and PIAS) DNA-binding domain [4]. The sample from the present patient contributes to the cloning of these translocation fusion partners.

  3. i(12p) in AML-M7 associated with mediastinal germ cell tumour.

A special type of AML-M7 is seen in Down's syndrome. The disease may present in the neonatal period and remits spontaneously, in which case the disorder is termed transient myeloproliferative disorder or transient abnormal myelopoiesis (TAM). Around a quarter of these cases recur later on in life into frank AML-M7, but typically respond well to a modified therapeutic regimen for childhood acute myeloid leukaemia. Recent evidence shows that AML-M7 occurring in a patient with a history of TAM may represent clonal evolution of the same disease [5].


  1. Tallman MS, Neuberg D, Bennett JM, Francois CJ, Paietta E, Wiernik PH, Dewald G, Cassileth PA, Oken MM, Rowe JM. Acute megakaryocytic leukemia: the Eastern Cooperative Oncology Group experience. Blood. 2000 Oct 1;96(7):2405-11.

  2. Nichols CR, Roth BJ, Heerema N, Griep J, Tricot G. Hematologic neoplasia associated with primary mediastinal germ-cell tumors. N Engl J Med. 1990 May 17;322(20):1425-9.

  3. Carroll A, Civin C, Schneider N, Dahl G, Pappo A, Bowman P, Emami A, Gross S, Alvarado C, Phillips C, et al. The t(1;22) (p13;q13) is nonrandom and restricted to infants with acute megakaryoblastic leukemia: a Pediatric Oncology Group Study.Blood. 1991 Aug 1;78(3):748-52.

  4. Ma Z, Morris SW, Valentine V, Li M, Herbrick JA, Cui X, Bouman D, Li Y, Mehta PK, Nizetic D, Kaneko Y, Chan GC, Chan LC, Squire J, Scherer SW, Hitzler JK. Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nat Genet 2001 Jul;28(3):220-1.

  5. Ma SK, Wan TS, Chan GC, Ha SY, Fung LF, Chan LC. Relationship between transient abnormal myelopoiesis and acute megakaryoblastic leukaemia in Down's syndrome. Br J Haematol 2001 Mar;112(3):824-5.

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