Al-Achkar Walid, Wafa Abdulsamad, Moassass Faten, Othman Moneeb Abdullah Kassem
Molecular Biology and Biotechnology Department, Human Genetics Division, Atomic Energy Commission, Damascus, Syria.
Mol Cytogenet. 2012 Aug 20;5(1):36. doi: 10.1186/1755-8166-5-36.
The so-called Philadelphia (Ph) chromosome is present in more than 90% of chronic myeloid leukemia (CML) cases. It results in juxtaposition of the 5' part of the BCR gene on chromosome 22 to the 3' part of the ABL gene on chromosome 9. Since the majority of CML cases are currently treated with Imatinib, variant rearrangements in general have no specific prognostic significance, although the mechanisms involved in resistance to therapy have yet to be investigated. The T315I mutation within the abl-gene is the most frequent one associated with resistance to tyrosine kinase inhibitors.
This study evaluated a Ph chromosome positive CML case resistant to imatinib mesylate. A dic(17;18), loss of TP53 gene, co-expression of b2a2 and b3a2 fusions transcript and a T315I mutation were found.
We reported here a novel case of a Ph chromosome positive CML with a secondary abnormality [dic(17;18)], resulting to Glivec resistance but good response to nilotinib. The dic(17;18) might be a marker for poor prognosis in CML. Our finding indicated for an aggressive progression of the disease. The patient died under the treatment due to unknown reasons.
在超过90%的慢性髓性白血病（CML）病例中存在所谓的费城（Ph）染色体。它导致22号染色体上BCR基因的5'部分与9号染色体上ABL基因的3'部分并列。由于目前大多数CML病例采用伊马替尼治疗，一般来说变异重排没有特定的预后意义，尽管与治疗耐药相关的机制尚待研究。abl基因内的T315I突变是与酪氨酸激酶抑制剂耐药相关的最常见突变。
本研究评估了一例对甲磺酸伊马替尼耐药的Ph染色体阳性CML病例。发现了一条双着丝粒染色体（17;18）、TP53基因缺失、b2a2和b3a2融合转录本的共表达以及一个T315I突变。
我们在此报告了一例具有继发性异常[双着丝粒染色体（17;18）]的Ph染色体阳性CML新病例，该病例导致对格列卫耐药但对尼洛替尼反应良好。双着丝粒染色体（17;18）可能是CML预后不良的一个标志物。我们的发现表明疾病进展迅速。该患者在治疗过程中因不明原因死亡。
