Totadri Sidharth, Singh Minu, Trehan Amita, Varma Neelam, Bhatia Prateek
1Pediatric Hematology-Oncology Unit, Department of Pediatrics, Advanced Pediatrics Center, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
2Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Indian J Hematol Blood Transfus. 2018 Oct;34(4):595-601. doi: 10.1007/s12288-018-0997-y. Epub 2018 Aug 1.
Philadelphia (Ph)-like or BCR-ABL like acute lymphoblastic leukemia (ALL) is defined on the basis of a gene expression profile that is similar to Ph-positive ALL. It comprises a wide spectrum of genetic lesions affecting primarily the cytokine receptor and/or kinase signalling genes. It accounts for approximately 10-15% of pediatric ALL, and is more common in patients who are high-risk according to the National Cancer Institute criteria. Presence of Ph-like mutations is an independent predictor of poor outcome. However, there is vast potential to utilize targeted therapy to improve survival in this group. The sizeable range of genetic lesions varying from translocations, fusions, point mutations and deletions make the diagnosis challenging. Hence, a practical and cost effective approach is required to enable identification in resource constrained settings. Patients with recurrent cytogenetic abnormalities such as ETV6-RUNX1, high hyperdiploidy, TCF3-PBX1, BCR-ABL1 and KMT2A (MLL) rearrangement need not be tested, as these are mutually exclusive with BCR-ABL like mutations. Detection of CRLF2 overexpression, which is the commonest abnormality, is employed as the first step. In patients lacking overexpression, testing for tyrosine kinase fusions can be performed. However, the goal should be to employ a combination of molecular diagnostic techniques such as reverse transcriptase polymerase chain reaction (PCR), real time quantitative PCR, fluorescence in situ hybridization and Sanger sequencing to detect genetic lesions that are amenable to targeted therapy.
费城（Ph）样或BCR-ABL样急性淋巴细胞白血病（ALL）是根据与Ph阳性ALL相似的基因表达谱来定义的。它包括广泛的遗传损伤，主要影响细胞因子受体和/或激酶信号基因。它约占儿童ALL的10%-15%，在根据美国国立癌症研究所标准属于高危的患者中更为常见。Ph样突变的存在是预后不良的独立预测因素。然而，利用靶向治疗来提高该组患者的生存率有很大潜力。从易位、融合、点突变和缺失等各种各样不同的遗传损伤使得诊断具有挑战性。因此，需要一种实用且具有成本效益的方法，以便在资源有限的环境中进行识别。对于存在复发性细胞遗传学异常的患者，如ETV6-RUNX1、高超二倍体、TCF3-PBX1、BCR-ABL1和KMT2A（MLL）重排，无需进行检测，因为这些与BCR-ABL样突变相互排斥。检测最常见异常CRLF2过表达作为第一步进行检测。对于缺乏过表达的患者，可以进行酪氨酸激酶融合检测。然而目标应该是采用多种分子诊断技术相结合，如逆转录聚合酶链反应（PCR）、实时定量PCR、荧光原位杂交和桑格测序，以检测适合靶向治疗的遗传损伤。
