6. Genetic characterization of tetraploid/near-tetraploid acute myeloid leukemia patients

Abstract

Myelodysplastic syndromes and acute myeloid leukemias are clonal malignant neoplasms arising from myeloid progenitors that are characterized by dysplasia, ineffective hematopoiesis, and variable numbers of blasts. Cytogenetic analysis plays a fundamental role in defining the genetic basis of these diseases and can aid in the risk stratification of MDS and AML patients. Tetraploidy is a rare cytogenetic finding among AML and MDS patients and much of what is known about this abnormality is based on single-case reports. To identify additional tetraploid or near-tetraploid AML or MDS patients we queried The Ohio State University Clinical Cytogenetics database. Since 2002, the cytogenetics laboratory analyzed a total of 2,039 MDS or AML patients, 38 of which harbored tetraploid or near-tetraploid clones (38/2,039 = 1.86%). We performed a retrospective analysis on this subset of patients by conducting a thorough review of their electronic medical records. In addition to standard demographic data, we present time-to-event outcomes such that the prognostic significance of this abnormality may be better understood. Furthermore, we utilized CytoGPS, a bioinformatic tool that parses karyotypes and quantifies the cumulative gains and losses across datasets, to identify recurrent abnormalities among this group of patients. Preliminary analysis demonstrates enrichment for poor prognostic indicators such as deletion of 5q, deletion of 7q, and deletion of 17p. Finally, in 16 of our 38 patients we describe molecular results (single gene or multi-gene panel) obtained at or near the time the patients presented with a tetraploid clone. This analysis aims to validate the poor prognosis associated with tetraploid or near-tetraploid AML and to better understand the co-occurrence of cytogenetic and molecular genetic abnormalities.