Brahmbhatt Manisha M, Trivedi Pina J, Patel Dharmesh M, Shukla Shilin N, Patel Prabhudas S
Cell Biology Division, The Gujarat Cancer and Research Institute, Asarwa, Ahmedabad-380016, India.
Medical Oncology Department, The Gujarat Cancer and Research Institute, Asarwa, Ahmedabad-380016, India.
J Assoc Genet Technol. 2014;40(1):4-9.
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.
慢性髓性白血病（CML）的特征是BCR/ABL融合基因的表达，这是一种组成型激活的酪氨酸激酶，通常由t(9;22)(q34;q11)或变异重排后形成的费城（Ph）染色体产生。Ph染色体的重复是疾病进展过程中反复出现的异常情况，而BCR/ABL的染色体内部扩增是一种罕见现象，并且与甲磺酸伊马替尼（IM）治疗耐药有关。在本研究中，我们使用G显带鉴定了Ph染色体同型等臂染色体的存在以及IM耐药患者中由克隆进化导致的t(3;21)(q26;q22)。使用双色双融合探针分析对间期和中期细胞核进行荧光原位杂交（FISH）证实了融合的BCR/ABL基因的扩增。我们的研究表明，CML的祖细胞通过Ph染色体的扩增作为对IM治疗耐药的一种机制而依赖于BCR/ABL。BCR/ABL与t(3;21)(q26;q22)以及RUNX1重排的共存可能在CML原始细胞转化中起关键作用。
