New recurrent balanced translocations in acute myeloid leukemia and myelodysplastic syndromes: Cancer and leukemia group B 8461

Abstract

Acquired chromosome abnormalities in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are among the most valuable determinants of diagnosis and prognosis. In search of new recurrent balanced translocations we reviewed the Cancer and Leukemia Group B (CALGB) cytogenetics database containing pretreatment and relapse karyotypes of 4,701 adults with AML and 565 with MDS who were treated on CALGB trials. We identified all cases with balanced structural rearrangements occurring as a sole abnormality or in addition to one other abnormality, excluded abnormalities known to be recurrent, and then reviewed the literature to determine whether any of what we considered unique, previously unknown abnormalities had been reported. As a result, we identified seven new recurrent balanced translocations in AML or MDS: t(7;11)(q22;p15.5), t(10;11)(q23;p15), t(2;12)(p13;p13), t(12;17)(p13;q12), t(2;3)(p21;p21), t(5;21)(q31;q22) and t(8;14)(q24.1;q32.2), and, additionally, t(10;12)(p11;q15), a new translocation in AML previously reported in a case of acute lymphoblastic leukemia. Herein we report hematologic and clinical characteristics, and treatment outcomes of patients with these newly recognized recurrent translocations. We also report 52 unique balanced translocations, together with the clinical data of patients harboring them, that to our knowledge have not been previously published. We hope that once the awareness of their existence is increased, some of these translocations may become recognized as novel recurring abnormalities. Identification of additional cases with both the new recurrent and the unique balanced translocations will enable determination of their prognostic significance and help to provide insights into the mechanisms of disease pathogenesis in patients with these rare abnormalities.

Rapid Evolution of a Myelodysplastic Syndrome in a Case of Multiple-Myeloma: Therapy Related or Not?

“…Treatment-related MDS is possible in this case, but patient-related factors cannot be excluded raising the question of the development of an independent second hematological malignancy. This is supported in part by the presence of MDS-related chromosomal anomalies [del(5q) [9] and t(2;12) [10]] in this patient. Regarding the short delay, the diagnosis was also perhaps prompted by the rapid decision to perform a control BM examination in front of cytopenias.…”

Acute myeloid leukemia with MYC rearrangement and JAK2 V617F mutation

“…The t(8;14)(q24;q32) in myeloid neoplasms is rare, described previously in five AML patients [6,10–12], with MYC assessed in only one [10]. Both cases showed rearrangement of chromosome band 8q24 on karyotypic analysis, which contains ~300 genes in addition to MYC [11][11][11].…”

“…MYC amplification, reported infrequently in AML with double minute chromosomes (dmin) or homogeneously staining regions (hsr)[3], is associated with drug resistance, disease progression, and poor survival [4,5]. Only five cases of myeloid neoplasms with t(8;14)(q24;q32) or one of the variant translocations have been reported previously [6]. Little is known about MYC dysregulation or MYC protein expression in myeloid malignancies.…”

Prognostic Impact of IPSS-R and Chromosomal Translocations in 751 Korean Patients with Primary Myelodysplastic Syndrome

“…However, since the identification and reporting of recurrent chromosomal translocations are essential to provide insights into the mechanisms of pathogenesis and identify genes involved in the pathogenesis of MDS, the role of cytogenetics including the study of genomic structure and function will remain important. Novel and recurrent translocations have been reported in a large series of patients [7,8]; however, only a few studies have addressed the prognostic impact of chromosomal translocations [9–11]. …”