Cytogenetic analysis of 280 patients with multiple myeloma and related disorders: Primary breakpoints and clinical correlations

Abstract

Cytogenetic analysis of unstimulated short‐term bone marrow cell cultures was performed on 280 patients with multiple myeloma and related disorders. In 65% of the cases, an additional short term B‐cell stimulated culture was also examined. Chromosomally abnormal clones were found in 31% of the patients, 15% in Waldenström macroglobulinemia, 25% in monoclonal gammopathies, 33% in multiple myeloma, and 50% in plasma cell leukemia. Three primary chromosomal breakpoints were recurrently involved: 14q32, 16q22, and 22q11. Structural rearrangements of chromosome I were the most frequent (26% of the abnormal cases), but always as a secondary change. Rearrangements of band 14q32 were found in 22% of the abnormal cases. Among the multiple myeloma patients who showed an abnormal karyotype, 33 (46%) were hyperdiploid, most frequently with 52–56 chromosomes, 29 patients (40%) were pseudodiploid, and the remaining 12 cases (14%) were hypodiploid. A highly significant relation was observed between the presence of an abnormal karyotype and the following clinical parameters: stage III (P = 0.0001), bone marrow plasma cell infiltration greater than 30% (P = 0.0001), presence of bone lesions (P = 0.0009), and β2‐microglobulin levels greater than 4 mg/L (P = 0.0001). Genes Chromosom. Cancer 18:84–93, 1997. © 1997 Wiley‐Liss, Inc.

Impaired NHEJ function in multiple myeloma

“…Multiple Myeloma is a disease that is characterized by gross and diverse genomic instability involving multiple chromosomes (1–6). To investigate repair pathway utilization in the three MM cell lines under study, we used the DNA-PK specific inhibitor, NU7026, to completely suppress the NHEJ pathway using a clonogenic cell survival as readout [32].…”

“…Malignant plasma cells in multiple myeloma (MM) often display aneuploidy and complex structural abnormalities associated with poor prognosis [1–4]. The immunoglobulin isotype switch region on chromosome 14q32 is frequently involved in translocations with several different partner chromosomes in MM [5,6].…”

Close relation between 14q32/IGH translocations and chromosome 13 abnormalities in multiple myeloma: a high incidence of 11q13/CCND1 and 16q23/MAF

“…Chromosome analyses are hampered by the low proliferation rate of PCs. Consequently, 50-70% of patients display a normal karyotype [13,15]. PCs with an abnormal karyotype elude detailed analysis because of the complex nature of the karyotypes and suboptimal banding quality.…”

NEK2 Induces Drug Resistance Mainly through Activation of Efflux Drug Pumps and Is Associated with Poor Prognosis in Myeloma and Other Cancers

“…Currently, the best marker for incurable myeloma is the presence of abnormal metaphase cytogenetics, but even its prognostic value is limited because its presence accounts for less than 30% of the observed variability in outcome of newly diagnosed patients (Calasanz et al, 1997). Using molecular genetic tools, such as fluorescence in situ hybridization (FISH) analysis, many of the partners involved in translocations with 14q32 (heavy chain gene locus) in myeloma have been identified (Avet-Loiseau et al, 2002).…”