Isodicentric Philadelphia chromosomes in imatinib mesylate (Gleevec)-resistant patients.
Amplification/duplication of the BCR-ABL gene has been found to be one of the key factors leading to drug resistance to imatinib mesylate (IM). In the present study, we used G-banding to identify the presence of de novo identical isodicentric chromosomes in IM-resistant patients. Fluorescence in situ hybridization (FISH) analysis on interphase nuclei confirmed the heterogeneity and amplification of the fused BCR-ABL gene. FISH analysis superimposed on G-banding confirmed the presence of isodicentric Philadelphia chromosomes. The impact of the isodicentric Philadelphia chromosomes on genomic instability, heterogeneity, and amplification of the Philadelphia chromosomes in IM-resistant patients is discussed.
Szych
Christine M
CM
Department of Pathology, University of Rochester, Strong Memorial Hospital, 601 Elmwood Avenue, P.O. Box 704, Rochester, NY 14642, USA.
Liesveld
Jane L
JL
Iqbal
M Anwar
MA
Li
LiQiong
L
Siebert
Susan
S
Asmus
Courtney
C
O'Malley
Julie
J
Lee
Adam
A
Wang
Nancy
N
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D002503:Centromere / Q000235:genetics; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate