Clinical diagnosis of adult patients with acute megakaryocytic leukemia

Abstract

Acute megakaryocytic leukemia (AMKL) is a rare subtype of acute myeloid leukemia (AML), which is challenging to diagnose due to frequent myelofibrosis (MF) and a low percentage of blast cells. In the present study, clinical characteristics and experimental observations in 9 adult patients diagnosed with AMKL, who were recruited by the Sino-U.S. Shanghai Leukemia Co-operative Group, were analyzed in order to summarize the diagnostic experience and provide recommendations on diagnosing AMKL. All the patients were diagnosed according to the 2008 World Health Organization diagnostic criteria. The mean age of the patients with AMKL was 59 years (range, 53-68 years). A total of 8 patients had different degrees of anemia, and 2 patients had <5% marrow blasts present in the bone marrow; however, the percentage of positive cells with cluster of differentiation (CD)41 and CD61 expression was >20%, as demonstrated by flow cytometry. A total of 6 patients were positive for platelet-specific antigens, as indicated by immunocytochemistry. Furthermore, 7 patients presented with moderate or marked MF, as demonstrated by a bone marrow biopsy. Karyotypic analysis indicated that 6 patients had abnormal karyotypes. Only 1 patient exhibited the Janus kinase 2V617F mutation. Treatment efficiency was notably poor, with a median survival time of 6.0 months (range, 1.1-24.0 months). In conclusion, the diagnosis of AMKL requires a combination of the results of bone marrow smears and bone marrow biopsy, immunophenotype or immunohistochemistry. We recommend that routine immunophenotypic analysis should include the CD41 and CD61 markers for diagnosing acute leukemia when bone marrow morphology does not indicate the diagnosis.

Keywords: acute megakaryocytic leukemia; diagnosis.

Figure 1.

Cell morphology observation of bone marrow smears. Megakaryoblasts often displayed different cell morphology in patients with AMKL (A) Megakaryoblasts frequently present with a cytoplasmic budding and groups of aggregated platelets, which also present with (B) marginal flocculence and (C) production of large platelets. The amount of cytoplasm is variable, frequently with (C) a pale blue coloration or (D) mauve staining pattern of the granules. The nucleus is round, oval or irregular in shape, and fine-granular heterochromatin is also observed.

Figure 2.

Immunohistochemical staining of bone marrow biopsy. (A) Immunocytochemical staining for factor VIII (magnification, ×60) demonstrates that the expression of the marker is frequently positive. (B) The cell indicated by the arrow displays distinct blebs of the cytoplasm or pseudopod formation, and glycoprotein IIb/IIIa (CD41) (magnification) is positive. (C) The two cells indicated by the arrow are large cells present with irregular shapes, the small cell has a high nuclear-cytoplasmic ratio resembling lymphoblasts. The glycoprotein IIIa (CD61) (magnification, ×100) staining of these cells is also positive. (D) Gomori staining frequently reveals myelofibrosis in patients with AMKL (magnification, ×60). AMKL, acute megakaryocytic leukemia; CD, cluster of differentiation.

Figure 3.

Amplification Refractory Mutation Screening assay to detect the JAK2V617F mutation in genomic DNA. Agarose electrophoresis analysis of the produced amplicons of the JAK2V617F gene mutation by reverse transcription-quantitative polymerase chain reaction. Patient no. 6 exhibited a mutant band, while other patients exhibited normal genotypes. JAK, Janus kinase.