Non-Random Chromosomal Rearrangements and Their Implications in Clinical Features and Outcome of Multiple Myeloma and Plasma Cell Leukemia

Abstract

Rearrangements of bands 14q32.3 and 19p13.3 and preferential deletion of the short arm of chromosome 1 were nonrandom chromosomal abnormalities in MM and PCL, warranting further investigation at the molecular level. From the viewpoint of clinical relevance, chromosome 14q32 translocation seems to be associated with leukemic manifestation, level of LDH, and shorter survival period from the time of chromosomal analysis. However, these results were obtained from patients with advanced disease, most of whom had already been treated with alkylating agents prior to cytogenetic analysis. To investigate the karyotypes of MM in the early stage and to determine correlations with clinical features, non-dividing cells should be analyzed. For this purpose, interphase FISH and/or comparative genomic hybridization are promising procedures to detect genomic alterations in early multiple myeloma.

Plasma cell leukemia: a highly aggressive monoclonal gammopathy with a very poor prognosis

“…Only three patients in both studies had hyperdiploidy (48,49, and 51 and 47, 54 and 86 chromosomes respectively). These results are in contrast with those published in MM, [27][28][29] in which hyperdiploidy is observed in approximately 60% of patients, but they confirm previously published analyses in PCL [8,30]. Analysis of rearrangements of the 14q32 region by FISH revealed significant differences with high cell mass MM-a higher incidence of t(11;14) (33 vs. 16%; p \ .025) and of t(14;16) (13 vs. 1%; p \ .002) though incidences of t(4;14) were identical and a higher incidence of monosomy 13 (68 vs. 42%; p = .005) [24].…”

Illegitimate switch recombinations are present in approximately half of primary myeloma tumors, but do not relate to known prognostic indicators or survival

“…2,[4][5][6][7][8][9] Despite the relatively small numbers of informative samples, our results confirmed the presence of illegitimate recombinations as an indication of IgH switch translocations in primary myeloma tumor. Using this basic molecular assay, the detection rate of 57% compared favorably with results from conventional cytogenetics (frequency of detection 10-40%), [10][11][12] for which insensitivity has been attributed to the difficulty in obtaining metaphases from infrequently dividing cells, and the telomeric location of the IgH genes and breakpoints. A different Southern blot assay designed to detect differences in migration of J and C fragments yielded a slightly lower rate of 25%.…”

“…[2][3][4][5][6][7][8][9] Conventional cytogenetics are relatively insensitive in the detection of switch translocations in myeloma, with an overall positivity rate of between 10% and 40%. [10][11][12] Using more sensitive molecular techniques, translocation breakpoints were initially identified in myeloma cell lines and confirmed in a limited number of primary tumors. 2,[4][5][6][7][8][9] The most common partner chromosomes and their candidate oncogenes are 11q13 (cyclin D1/bcl-1), 4 4p16 (FGFR3 and MMSET or WHSC1), 5,7,9,13 6p25 (IRF4), 8 and 16q23 (c-maf ).…”

Aggressive neoplastic plasma cell growth with MLL gene rearrangement after high-dose therapy with autologous stem cell support for multiple myeloma

“…Recently, many cytogenetic abnormalities have been found in MM cells by the FISH method. 12 These findings suggest that investigation of MLL gene abnormalities by Southern blot or FISH methods is very important in understanding the effects of etoposide, even if karyotypic aberrations are not detected in MM patients who received PBSCT.…”