Biology, clinical, and hematologic features of acute megakaryoblastic leukemia in children

Abstract

To assess the incidence, clinical features at presentation, hematologic, immunophenotypic, and cytogenetic characteristics of AMKL in children we prospectively studied 834 consecutive non selected children with newly diagnosed acute leukemia (AL) admitted to the Hematology Department at the Instituto Nacional de Pediatría (INP), Mexico, D.F. We found 682 cases (81.8%) with a typical ALL immunophenotype, and the remaining 152 (18.2%) were considered to have AML. In 29 of the 152 patients with AML studied, a diagnosis of AMKL was established. These 29 cases represented 19.1% of the cases of AML and 3.48% of the total cases of AL during the time span covered by the study. Twenty-four percent of the cases occurred in infants 2 years old or younger and 41.4% occurred in children 41 months of age or younger. In contrast, in only 18.6% of the patients with AML (M0-M6), the diagnosis was established before 42 months of age and in 17% before their second year of life. Clinical presentation was not strikingly different than that observed in patients with other types of AML, and the time interval from onset of symptoms to diagnosis was also similar, though in a small subset of patients, the clinical course was characterized by a chronic slowly progressive disorder extending over weeks or months resembling smoldering leukemia or chronic myelofibrosis with agnogenic myeloid metaplasia. Bone marrow (BM) fibrosis was a constant features in our patients; 75% of the patients studied showed this complication at the time of diagnosis. Some rather unusual findings in this study were intense skeletal pains from multiple osteolytic lesions, the presence of soft-tissue tumor, and the presence of cohesive scanty clusters of primitive-looking blast cells in BM aspirates. Several interesting cytogenetic findings in our study were t(1;22)(p13;q13) in a 14-year-old boy, t(9;22)(q34;q11) in one patient, and monosomy 7 in two patients. Another important finding in our study was the clinical association with colonic adenocarcinoma in one patient, an association that to our knowledge has not been reported previously. In conclusion, our data suggest that the incidence of AMKL in Mexico might be higher than those reported in Caucasian white pediatric population, and that biologic and cytogenetic profile may differ from those of western countries, but more studies are needed to corroborate cytogenetic heterogeneity, ethnic and geographic diversity. Early onset of the disease, low WBC counts, slight thrombocytopenia or normal platelet counts, and BM fibrosis were characteristic distinctive features of at least half of the patients with this subtype of AML. Am. J. Hematol. 73:71-80, 2003.

Activating mutations in human acute megakaryoblastic leukemia

“…1 Approximately 65% of AMKLs are associated with myelofibrosis. 1,2 In adults, AMKL is frequently observed as secondary leukemia after chemotherapy or leukemic transformation of several chronic myeloproliferative disorders (MPDs) including chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis (IMF). [3][4][5] Recently, point mutations have been described within the JAK2 gene in MPD and within the gene coding for the thrombopoietin receptor (MPL) in a subset of myelofibrosis and ET.…”

JAK2T875N is a novel activating mutation that results in myeloproliferative disease with features of megakaryoblastic leukemia in a murine bone marrow transplantation model

“…The estimated frequency of AMKL varies between studies, perhaps due to a reliance on morphology for diagnostic criteria, but ranges from 3% to 14% of AML, and is more frequent in children than in adults. [1][2][3] In adults, AMKL is also frequently observed as secondary leukemia after chemotherapy or leukemic transformation of several chronic myeloproliferative syndromes including chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis (IMF). [4][5][6][7] Approximately 65% of AMKLs are associated with myelofibrosis.…”

The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model

“…Acute megakaryoblastic leukemia (AMKL) is a heterogeneous subtype of acute myeloid leukemia (AML) and is more frequent in children than in adults (1)(2)(3). The molecular basis of AMKL is poorly understood in adults, whereas 2 major molecular subtypes are recognized in pediatric AMKL.…”