编者按：研究表明慢性淋巴细胞白血病（CLL）中激酶突变较为少见，因此靶向作用于信号途径的激酶抑制剂在B细胞进展中至为重要，尤其是靶向作用于B细胞受体(BCR)的相关已经引起了临床显著疗效。在本届ASCO年会上，美国俄亥俄州立大学医学中心Jeffrey A. Jones教授受邀做了关于回顾靶向治疗CLL的激酶抑制剂的临床进展的专题报告。会后，《肿瘤瞭望》对Jones教授进行了专访。

美国俄亥俄州立大学医学中心Jeffrey A. Jones教授

 　　Oncology Frontier: Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia and is characterized by a highly variable clinical course. In the past decade， what are the prognostic risk factors that have been identified facilitating the classification of CLL into various risk groups?

　　《肿瘤瞭望》：慢性淋巴细胞白血病是成人中最常见的白血病，临床病程有很大的异质性。近年来，有哪些预后风险因素有助于将CLL进行不同危险度的分期？

 

　　Dr Jones: There are two commonly obtained genetic risk features in the initial evaluation of CLL that large centers (like ours at Ohio State University Medical Center) routinely obtain. The first is to determine the somatic hypermutation status of the immunoglobulin heavy chain (IGH) gene. For the last twenty years now， we have understood that patients whose CLL has a mutated immunoglobulin heavy chain gene have a more favorable prognosis than patients who have an unmutated immunoglobulin heavy chain gene. We have come to understand more recently that that likely has to do with the dependence of CLL cells on B-cell receptor signaling. We also commonly obtain interphase cytogenetics or FISH to look for recurrent cytogenetic abnormalities of known prognostic significance. There is a standard panel available at our institution and many commercial labs that allows us to characterize patients no only for their ultimate prognosis at diagnosis， but also more (and increasingly) importantly， their susceptibility to certain types of therapy. These FISH results are important now as we select therapies. For example， we know that patients with a deletion of the short arm of chromosome 17p， lose some of the function of the p53 gene which is very important in maintaining sensitivity to chemotherapy. Those are patients who absolutely should be treated with a non-chemotherapy regimen if at all feasible， as the prognosis with chemotherapy-based treatments is impaired.

　　Jones教授：目前广泛认可的CLL的初始评估主要有2种。第一种是IGH基因体细胞突变。过去十几年中，IGH基因突变的患者预后远远好于非突变人群已得到共识。第二种是常规应用FISH去检测常见的细胞遗传学的突变，以评估其对于预后的影响。目前我们中心有标准化的流程去研究患者的预后和患者更适合哪一种药物去治疗。FISH的结果是十分重要的，例如，del（17p）的患者，会失去p53基因的功能，而p53(+)的患者对很多化疗药物敏感，所有对del（17p）的患者如果疾病稳定，是应该接受非化疗方案的治疗。

 

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