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BCR-ABL gene amplification and overexpression in a patient with chronic myeloid leukemia treated with imatinib
- Source :
- Cancer Genetics and Cytogenetics. 159:164-167
- Publication Year :
- 2005
- Publisher :
- Elsevier BV, 2005.
-
Abstract
- Imatinib mesylate was designed as an inhibitor targeting the BCR-ABL tyrosine kinase, the molecular counterpart of the Philadelphia translocation t(9;22)(q34;q11). We report on a patient with chronic myeloid leukemia (CML) undergoing acceleration during imatinib treatment. Cytogenetic analysis revealed four different cell populations: 46,XX,t(9;22)(q34;q11),der(18)t(2;18)(p11;p11)[1]/47,idem,i(17)(q10),-der(18)t(2;18),+der(22)t(9;22)[1]/46,idem,-t(9;22),der(9)t(9;22),ider(22)t(9;22)[12]/ 47,idem,-t(9;22),der(9)t(9;22),+22,ider(22)t(9;22)x2[1]. FISH analysis confirmed the presence of these four clones. Moreover, 49% of the interphase nuclei contained either one or two clustered fusion signals, indicating a low-level amplification of the BCR-ABL fusion gene. With quantitative real-time RT-PCR, a BCR-ABL/G6PDH ratio of 0.8 was determined, which is comparable to that measured in the K562 cell line with a known BCR-ABL amplification and which is increased by more than about 60-fold compared to a CML at diagnosis with >80% Philadelphia-positive cells. We give further evidence that the genomic BCR-ABL amplification results in an increased level of BCR-ABL transcript linking two potent mechanisms of resistance against imatinib treatment.
- Subjects :
- Cancer Research
Fusion Proteins, bcr-abl
Antineoplastic Agents
Biology
Piperazines
Translocation, Genetic
Fusion gene
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
hemic and lymphatic diseases
Genetics
medicine
Humans
Molecular Biology
In Situ Hybridization, Fluorescence
Aged
Chromosome Aberrations
ABL
Gene Amplification
Intracellular Signaling Peptides and Proteins
Myeloid leukemia
Imatinib
medicine.disease
Molecular biology
Leukemia
Pyrimidines
Imatinib mesylate
Drug Resistance, Neoplasm
Karyotyping
Benzamides
Immunology
Imatinib Mesylate
Female
Tyrosine kinase
K562 cells
medicine.drug
Subjects
Details
- ISSN :
- 01654608
- Volume :
- 159
- Database :
- OpenAIRE
- Journal :
- Cancer Genetics and Cytogenetics
- Accession number :
- edsair.doi.dedup.....80158d825b8220e9e6c694e281484cf6