Ahmed Makhdum, Zhang Leo, Nomie Krystle, Lam Laura, Wang Michael
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
The University of Texas Health Science Centre, Houston, Texas, USA.
Oncotarget. 2016 Sep 6;7(36):58638-58648. doi: 10.18632/oncotarget.10716.
Mutations and epigenetic alterations are key events in transforming normal cells to cancer cells. Mantle cell lymphoma (MCL), a non-Hodgkin's lymphoma of the B-cell, is an aggressive malignancy with poor prognosis especially for those patients who are resistant to the frontline drugs. There is a great need to describe the molecular basis and mechanism of drug resistance in MCL to develop new strategies for treatment. We reviewed frequent somatic mutations and mutations involving the B-cell pathways in MCL and discussed clinical trials that attempted to disrupt these gene pathways and/or epigenetic events. Recurrent gene mutations were discussed in the light of prognostic and therapeutic opportunity and also the challenges of targeting these lesions. Mutations in the ATM, CCND1, TP53, MLL2, TRAF2 and NOTCH1 were most frequently encountered in mantle cell lymphoma. Translational models should be built that would assess mutations longitudinally to identify important compensatory, pro-survival and anti-apoptic pathways and actionable genetic targets.
突变和表观遗传改变是将正常细胞转变为癌细胞的关键事件。套细胞淋巴瘤（MCL）是一种B细胞非霍奇金淋巴瘤，是一种侵袭性恶性肿瘤，预后较差，尤其是对那些对一线药物耐药的患者。非常需要描述MCL中耐药的分子基础和机制，以开发新的治疗策略。我们回顾了MCL中常见的体细胞突变和涉及B细胞途径的突变，并讨论了试图破坏这些基因途径和/或表观遗传事件的临床试验。根据预后和治疗机会以及靶向这些病变的挑战，对复发性基因突变进行了讨论。ATM、CCND1、TP53、MLL2、TRAF2和NOTCH1的突变在套细胞淋巴瘤中最为常见。应该建立翻译模型，纵向评估突变，以识别重要的代偿、促生存和抗凋亡途径以及可操作的基因靶点。
