Cytogenetic profile of childhood and adult megakaryoblastic leukemia (M7): a study of the Groupe Francais de Cytogenetique Hematologique (GFCH)

Abstract

on behalf of the Groupe Français de Cytogénétique Hématologique (GFCH) and with the contribution of the Groupe Français d'Hématologie Cellulaire (GFHC)To draw the cytogenetic profile of childhood and adult acute megakaryoblastic leukemia (M7), the Groupe Franç ais de Cytogéné tique Hé matologique collected 53 cases of M7 (30 children and 23 adults). Compared to other acute myeloid leukemias, M7 is characterized by a higher incidence of abnormalities, a higher complexity of karyotypes, and a different distribution of abnormalities among children and adults. Nine cytogenetic groups were identified: normal karyotypes (group 1), patients with Down syndrome (group 2), numerical abnormalities only (group 3), t(1;22)(p13;q13) or OTT-MAL transcript (group 4), t(9;22)(q34;q11) (group 5), 3q21q26 (group 6), ؊5/del(5q) or ؊7/ del(7q) or both (group 7), i(12)(p10) (group 8), and other structural changes (group 9). Groups 1, 2, 3, and 4 were exclusively composed of children (except one adult in group 3), whereas groups 5, 6, 7, and 8 were mainly made up of adults. The main clinical and hematologic features of these groups were described. No new recurrent abnormality was identified, but mapping of all breakpoints allowed us to specify several possible hot spots of rearrangement: 17q22-23, 11q14-21, 21q21-22, and 16q21-22-23. Although 90.5% of cases had no documented antecedent hematologic disorder or exposure to chemotherapy or radiotherapy, the morphologic and the cytogenetic findings indicated that M7 might be a secondary leukemia more often than suggested by preceding history, particularly among adults. The concurrent analyses of morphologic and cytogenetic data also led us to assume that the initial precursor involved might be more immature in adult than in childhood M7. (Blood. 2002;100:618-626)

Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling

“…Treatment outcome is more favorable in DS-AMKL compared with non-DS individuals (1,2). Discovery of molecular mechanisms involved in AMKL and identification of prognostic factors have been limited because of heterogeneity of the recurrent cytogenetic lesions involved (3). One defined entity is the infant form characterized by the recurrent translocation t(1;22) in non-DS patients (4,5).…”

RBM15-MKL1 (OTT-MAL) fusion transcript in an adult acute myeloid leukemia patient

“…RT-PCR and sequence data support the presence of this abnormal fusion transcript in our patient. Therefore, the +der(1)t(1;22)(p13,q13) reported in this case represents an RBM15-MKL1 (OTT-MAL) fusion transcript or, alternatively, a cryptic translocation of this abnormality, similar to cases with an OTT-MAL fusion transcript and normal karyotype [10,11]. Our FISH data show that material from chromosome 22 was translocated to the derivative chromosome 1.…”

“…It is restricted to young patients with AMKL, who are responsive to intensive chemotherapy [10,11]; however, it is also a poor prognosis predictor in some patients [2][3][4][5]. Our patient's clinical characteristics are very different from those reported in the literature: he is an adult, and he had M1 morphology as opposed to the characteristic M7.…”

A novel fusion of RBM6 to CSF1R in acute megakaryoblastic leukemia

“…It is characterized by complex karyotypes, and the clinical and morphologic diagnosis can be difficult due in part to low blast counts in the peripheral blood, severe bone marrow fibrosis that impairs acquisition of bone marrow aspirates for analysis, and lack of molecular markers of disease. 18,19 To facilitate the rapid identification of the potential tyrosine kinases activated in leukemia cells, we used a phosphoproteomic approach that led to the identification of a novel fusion tyrosine kinase involving CSF1R in the acute megakaryoblastic leukemia cell line MKPL-1. This approach is a sensitive and reproducible functional strategy to identify activated protein kinases and their phosphorylated substrates without prior knowledge of the signaling networks.…”