Cytogenetic findings in adult acute leukemia and myeloproliferative disorders with an involvement of megakaryocyte lineage

Abstract

Cytogenetic analyses were performed on 12 adult patients with abnormal megakaryoblastic proliferation which was detected by ultrastructural cytochemical study (platelet peroxidase) and platelet-megakaryocytes-specific monoclonal antibodies (TP-80, Plt1, AN51, and KOR-77). The patients consisted of two patients with myelodysplastic syndromes (MDS), three with acute megakaryoblastic leukemia (AMKL), six with megakaryoblastic transformation in Philadelphia-positive chronic myelogenous leukemia (CML-meg-BC), and one case of chronic myeloproliferative disorder (CMPD). Among them, an inversion of the long arm of chromosome 3 [inv(3)(q21q26)] was found in one AMKL patient with a normal platelet count. Chromosome change at band 3q26 was also found in one MDS patient without thrombocythemia. Furthermore, the long arm of chromosome 13, where rearrangements in myelofibrosis are clustered (13q12----q22) was seen in one MDS patient. Trisomoy of chromosome 19 was found in one AMKL patient and three CML-meg-BC patients. These findings indicate that cytogenetic abnormalities involving 3q26, 13q, and trisomy 19 are associated with hematologic neoplasia with megakaryocytic lineage in adult patients, although these abnormalities were not related to the survival of the patients. During the period of this study, two acute myelogenous leukemia patients (AML-M2 and AML-M5b) with chromosome rearrangements at band 3q21 and thrombocythemia were found, indicating that chromosome abnormality at band 3q21 is related to quantitative platelet dysfunction, whereas that at 3q26 is related to hematologic malignancies with a proliferation of megakaryocytic lineage.

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

“…[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. 2 Our understanding of the molecular basis of AMKL has progressed over the past several years.…”

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

“…This frequency is in agreement with prior reports indicating incidences of 16%, 19%, and 25% in adult M7. 4,5,7 The incidence of 3q aberrations in M7 is higher than in de novo AMLs (2%) and secondary AMLs (5%). 30 Ph chromosome was as frequent as 3q abnormalities, representing 17% of adult M7.…”

“…In previous reports, the incidence of t(9;22) in M7 has widely varied from 0% in Lu et al's, to 16% in Cuneo et al's and 66% in Ohyashiki et al's studies. 4,5,7 This variability might reflect registration bias, that is, inclusion or noninclusion of blastic phases of CML. Even if its genuine incidence is difficult to assess in M7, t(9;22) is probably more frequent in this subgroup than in de novo AML as a whole, in which approximately 1% of patients are Ph ϩ .…”

“…[4][5][6] The only study comprising both childhood and adult M7 was that reported by Lu et al who reviewed all cases with documented cytogenetic data published before 1993. 7 These previous studies revealed evidence for cytogenetic heterogeneity among cases with acute megakaryoblastic leukemia.…”

De novo acute megakaryoblastic leukemia with p210 BCR/ABL and t(1;16) translocation but not t(9;22) Ph chromosome

“…Ph chromosome is a rare cytogenetic abnormality (≈ 1%) in AML [5,6]. The incidence of t(9;22) in AMKL varies considerably in the literature: from < 20% to > 60%, possibly due to inconsistency in the inclusion/exclusion of blastic phase of chronic myeloid leukemia (CML)[7-9]. …”