Agirre Xabier, Román-Gómez José, Vázquez Iria, Jiménez-Velasco Antonio, Larráyoz María J, Lahortiga Idoya, Andreu Enrique J, Márquez José, Beltrán de Heredia José M, Odero María D, Prósper Felipe, Calasanz María J
Area of Cancer, Area of Cell Therapy and Hematology Service, University Clinic, University of Navarra and Foundation for Applied Medical Research, Avda. Pio XII 36, Pamplona, Spain.
Cancer Genet Cytogenet. 2005 Jul 1;160(1):22-6. doi: 10.1016/j.cancergencyto.2004.11.010.
In this study, we report the case of a Philadelphia (Ph) positive chronic myelogenous leukemia (CML) patient with the presence of p190 and p210 BCR-ABL1 mRNA fusion transcripts derived from e1a2 and b3a2 BCR-ABL1 genomic rearrangements, respectively. The presence of e1a2 BCR-ABL1 genomic rearrangement was seen in 2 different clones, one with the rearrangement and another one with the rearrangement and deletion of the BCR gene of the non-rearranged chromosome 22. After treatment with imatinib, the p210 transcript could not be detected, whereas p190 was still present 6 months after initiation of imatinib therapy and progression to blast phase. The absence of p210 transcript post treatment indicates that the clone with b3a2 responded to imatinib and that the observed resistance was associated to cells harboring the e1a2 genomic rearrangement. Despite resistance of this patient to imatinib, no evidence of mutations in the kinase domain of ABL1 was found. Loss of normal BCR in one cell clone may contribute to the resistance to imatinib due to the lack of BCR mediated inhibition of BCR-ABL1.
在本研究中，我们报告了一例费城（Ph）阳性慢性髓性白血病（CML）患者，其存在分别源自e1a2和b3a2 BCR-ABL1基因组重排的p190和p210 BCR-ABL1 mRNA融合转录本。在2个不同克隆中发现了e1a2 BCR-ABL1基因组重排，一个克隆存在重排，另一个克隆存在重排且未重排的22号染色体上的BCR基因发生缺失。使用伊马替尼治疗后，无法检测到p210转录本，而在伊马替尼治疗开始并进展至急变期6个月后，p190仍然存在。治疗后p210转录本的缺失表明携带b3a2的克隆对伊马替尼有反应，且观察到的耐药性与携带e1a2基因组重排的细胞有关。尽管该患者对伊马替尼耐药，但未发现ABL1激酶结构域存在突变的证据。一个细胞克隆中正常BCR的缺失可能由于缺乏BCR介导的对BCR-ABL1的抑制作用而导致对伊马替尼耐药。
