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Chromosome abnormalities clustering and its implications for pathogenesis and prognosis in myeloma

Abstract

The nonrandom recurrent nature of chromosome abnormalities in myeloma suggests a role for them in disease pathogenesis. We performed a careful cytogenetic analysis of patients with abnormal karyotypes (n = 254), to discern patterns of association, search for novel abnormalities and elucidate clinical implications. Patients with karyotypic abnormalities suggestive of myelodysplasia/acute leukemia were excluded. In this study we compared survival by abnormality only between patients with abnormal karyotypes. Patients with abnormalities were more likely to have features of aggressive disease as compared to all other patients without abnormalities entered into the myeloma database (lower hemoglobin, higher β2-microglobulin, labeling-index and plasmocytosis; all P < 0.0001). Several groups of patients could be readily identified; hypodiploid (22%), pseudodiploid (36%), hyperdiploid (31%) and near-tetraploid (11%). Clustering associations were seen among several trisomies and monosomy of chromosome 13 and 14. Several monosomies (−2, −3, −13, −14 and −19), 1p translocations/ deletions, and hypodiploidy were associated with a significantly shorter survival. Trisomy of chromosome 13 was rare (<2%). Even among patients with abnormal karyotypes, specific chromosome abnormalities can impart biologic variability in myeloma, including several monosomies, hypodiploidy and abnormalities of 1p.

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Acknowledgements

RF is a Clinical Investigator of the Damon Runyon Cancer Research Fund and a Leukemia and Lymphoma Society Translational Research Awardee. This work was supported in part by Public Health Service grant no. R01 CA83724-01 (RF) and P01 CA62242 (RAK, PRG, TEW, JAL) from the National Cancer Institute, and the ‘Foundation to Cure Myeloma’ supports RF and PRG. PRG is supported by the ECOG grant CA21115-25C from the National Cancer Institute.

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Debes-Marun, C., Dewald, G., Bryant, S. et al. Chromosome abnormalities clustering and its implications for pathogenesis and prognosis in myeloma. Leukemia 17, 427–436 (2003). https://doi.org/10.1038/sj.leu.2402797

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