BCR/ABL amplification in chronic myelocytic leukemia blast crisis following imatinib mesylate administration.
The onset of accelerated phase or blast crisis of chronic myelocytic leukemia (CML) is usually associated with the acquisition of new chromosome abnormalities in addition to the t(9;22)(q34;q11) that is characteristic of the chronic phase CML. We describe the cytogenetic and molecular genetic findings in two cases of myelocytic blast crisis of CML, one occurring 6 months after commencing treatment with the ABL-specific tyrosine kinase inhibitor imatinib mesylate (STI571, Glivec, or Gleevec) and the second treated with imatinib mesylate for established blast crisis. In both cases, multiple secondary cytogenetic abnormalities were observed at transformation, with homogeneously staining regions that were shown to contain BCR/ABL amplification by fluorescence in situ hybridization appearing after imatinib mesylate administration. BCR/ABL amplification is emerging as an important mechanism of acquired resistance to imatinib mesylate.
Campbell
Lynda J
LJ
Victorian Cancer Cytogenetics Service, St. Vincent's Hospital, Melbourne, Fitzroy VIC 3065, Australia. campbelj@svhm.org.au
Patsouris
Crisoula
C
Rayeroux
Kathleen C
KC
Somana
Kathy
K
Januszewicz
E Henry
EH
Szer
Jeffrey
J
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D001752:Blast Crisis / Q000235:genetics*; D001854:Bone Marrow Cells / Q000473:pathology; D002871:Chromosome Banding; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D005784:Gene Amplification; D006801:Humans; D000068877:Imatinib Mesylate; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl