Ladha Abdullah, Zhao Jianzhi, Epner Elliot M, Pu Jeffrey J
1Upstate Cancer Center, State University Of New York Upstate Medical University, SUNY Upstate Cancer Center, Suite 331, CWB, 750 E. Adams Street, Syracuse, NY 13210 USA.
2Penn State Hershey Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033 USA.
Exp Hematol Oncol. 2019 Jan 30;8:2. doi: 10.1186/s40164-019-0126-0. eCollection 2019.
Mantle cell lymphoma is a relatively new recognized hematological malignant disease, comprising of 2.5-6% non-Hodgkin's lymphomas. The complexity of its clinical presentations (nodular pattern, diffuse pattern, and blastoid variant), variety in disease progression, and treatment response, make this disease a research focus to both experimental oncology and clinical oncology. Overexpression of cyclin D1 and chromosome t(11,14) translocation are the known molecular biomarkers of this disease. Mantle cell international prognostic index (MIPI), ki-67 proliferation index, and mutation are emerging as the prognostic biomarkers. Epigenetic profile variance and gene expression profile correlate with treatment response. Over the years, the treatment strategy has been gradually evolving from combination chemotherapy to combination of targeted therapy, epigenetic modulation therapy, and immunotherapy. In a surprisingly short period of time, FDA specifically approved 4 drugs for treating mantle cell lymphoma: lenalidomide, an immunomodulatory agent; Bortezomib, a proteasome inhibitor; and Ibrutinib and acalabrutinib, both Bruton kinase inhibitors. Epigenetic agents (e.g. Cladribine and Vorinostat) and mTOR inhibitors (e.g. Temsirolimus and Everolimus) have been showing promising results in several clinical trials. However, treating aggressive variants of this disease that appear to be refractory/relapse to multiple lines of treatment, even after allogeneic stem cell transplant, is still a serious challenge. Developing a personalized, precise therapeutic strategy combining targeted therapy, immunotherapy, epigenetic modulating therapy, and cellular therapy is the direction of finding a curative therapy for this subgroup of patients.
套细胞淋巴瘤是一种相对较新被认识的血液系统恶性疾病，占非霍奇金淋巴瘤的2.5 - 6%。其临床表现的复杂性（结节型、弥漫型和母细胞样变异型）、疾病进展的多样性以及治疗反应，使该疾病成为实验肿瘤学和临床肿瘤学的研究重点。细胞周期蛋白D1的过表达和染色体t(11,14)易位是该疾病已知的分子生物标志物。套细胞国际预后指数（MIPI）、Ki-67增殖指数和基因突变正逐渐成为预后生物标志物。表观遗传学特征差异和基因表达谱与治疗反应相关。多年来，治疗策略已从联合化疗逐渐演变为靶向治疗、表观遗传调节治疗和免疫治疗的联合应用。在令人惊讶的短时间内，美国食品药品监督管理局（FDA）专门批准了4种治疗套细胞淋巴瘤的药物：来那度胺，一种免疫调节剂；硼替佐米，一种蛋白酶体抑制剂；以及伊布替尼和阿卡替尼，两者均为布鲁顿激酶抑制剂。表观遗传药物（如克拉屈滨和伏立诺他）和mTOR抑制剂（如替西罗莫司和依维莫司）在多项临床试验中已显示出有前景的结果。然而，治疗该疾病的侵袭性变异型，即使在异基因干细胞移植后，对多线治疗似乎难治/复发，仍然是一个严峻的挑战。制定一种结合靶向治疗、免疫治疗、表观遗传调节治疗和细胞治疗的个性化、精准治疗策略，是为这一亚组患者找到治愈性疗法的方向。
