Comparative genomic hybridization analysis of Japanese B-cell chronic lymphocytic leukemia: correlation with clinical course

Abstract

B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in Westerners. By contrast, B-CLL is rare in Asians, including Japanese. We applied comparative genomic hybridization (CGH) to screen 26 newly diagnosed Japanese B-CLL patients for genomic aberrations. Chromosomal imbalances were detected in 12 of the 26 cases (46%). The most frequent changes observed were gains of chromosomes 3q in five cases (19%) and 17q in three cases (12%). Other recurrent imbalances included gains of chromosomes 8q, 18q and losses of chromosomes 13q and 17p. Samples obtained at different sites disclosed identical CGH findings in all of the three cases examined. Genomic imbalances as detected by CGH were associated with disease progression and shorter survival. Two patients, with chromosomal imbalances, including gains of both 3q and 18q, developed large cell transformation of the disease within 4 years. In conclusion, CGH abnormality was associated with poor prognosis in Japanese B-CLL, and features of Japanese B-CLL, compared to chromosomal abnormalities of Western B-CLL in the literature, include a lower incidence of any abnormality in particular regarding gain of 12q, with the exception of a higher incidence of gains at 3q.

The mystery of chronic lymphocytic leukemia (CLL): Why is it absent in Asians and what does this tell us about etiology, pathogenesis and biology?

“…More sensitive analyses using gene-chip arrays detect similar incidences of most genetic abnormalities in persons of predominately European descent and Asians with CLL except for +3/dup(3q) and +18/dup(18q) with a higher frequency in Asians with CLL [34]. +3 detected by comparative genomic hybridization (CGH) or FISH is reported 1-3% in persons of predominately European descent with CLL which seems lower than the 6-19% reported in Asians with CLL [30,35]. In a study of Taiwanese with CLL, persons with + 3 had early-stage disease but brief survival [30].…”

Novel genomic alterations and clonal evolution in chronic lymphocytic leukemia revealed by representational oligonucleotide microarray analysis (ROMA)

“…11,14 CGH can detect novel lesions, ascertain the frequencies of gains and losses with greater accuracy, and pinpoint candidate genes associated with the disease within known regions of recurrent abnormality. [33][34][35][37][38][39] Therefore, on the basis of previous experiences, 14,40,41 it was reasonable to expect that increased resolution would yield more accurate delineation of previously described lesions as well as identification of new ones.…”

Array CGH in Human Leukemia: From Somatics to Genetics

“…Analysis of CLL patients using genomic arrays revealed known losses of 13q, 11q and gains of 12q and, in addition, defined commonly affected regions more precisely [Tsukasaki et al, 2006;Tyybakinoja et al, 2007b]. In a study using a bacterial artificial chromosome (BAC) array, in combination with an oligonucleotide array for confirmation of the acquired data, genomic changes involving loci of prognostic significance were detected at the expected frequencies in 89% of 174 CLL cases [Gunn et al, 2008].…”