title: Multiple Copies of BCR/ABL Fusion Signals and t(3;21) in a Chronic Myeloid Leukemia: Patient with Blast Crisis - A Rare Event with Imatinib Mesylate (Gleevec)-Resistance in an Indian Patient.
abstract: Chronic myeloid leukaemia (CML) is characterized by the expression of BCR/ABL fusion gene, a constitutively activated tyrosine kinase that commonly results from the formation of the Philadelphia (Ph) chromosome after a t(9;22)(q34;q11) or variant rearrangement. The duplication of Ph chromosome is a recurring abnormality acquired during disease progression, whereas intrachromosomal amplification of BCR/ABL is a rare phenomenon and has been associated with imatinib mesylate (IM) therapy resistance. In the present study, we used G-banding to identify the presence of identical isochromosomes of the Ph chromosome and t(3;21)(q26;q22) resulted from clonal evolution in IM-resistant patient. Fluorescence in situ hybridization (FISH) using dual color dual fusion probe analysis on interphase and metaphase nuclei confirmed the amplification of the fused BCR/ABL gene. Our study indicated that the progenitor of CML was BCR/ABL dependent through the amplification of Ph chromosome as a mechanism of resistance to IM therapy. The coexistence of BCR/ABL and t(3;21)(q26;q22) with RUNX1 rearrangement might play a pivotal role in the CML blast transformation.
authors.affiliation: Cell Biology Division, The Gujarat Cancer and Research Institute, Asarwa, Ahmedabad-380016, India.
authors.forename: Manisha M
authors.initials: MM
authors.lastname: Brahmbhatt
authors.affiliation: Cell Biology Division, The Gujarat Cancer and Research Institute, Asarwa, Ahmedabad-380016, India.
authors.forename: Pina J
authors.initials: PJ
authors.lastname: Trivedi
authors.affiliation: Cell Biology Division, The Gujarat Cancer and Research Institute, Asarwa, Ahmedabad-380016, India.
authors.forename: Dharmesh M
authors.initials: DM
authors.lastname: Patel
authors.affiliation: Medical Oncology Department, The Gujarat Cancer and Research Institute, Asarwa, Ahmedabad-380016, India.
authors.forename: Shilin N
authors.initials: SN
authors.lastname: Shukla
authors.affiliation: Cell Biology Division, The Gujarat Cancer and Research Institute, Asarwa, Ahmedabad-380016, India.
authors.forename: Prabhudas S
authors.initials: PS
authors.lastname: Patel