Characterizing Clonogenic Populations in Mantle Cell Lymphoma

描述（由申请人提供）：血液恶性肿瘤和许多实体肿瘤都含有肿瘤启动细胞亚群，这些细胞对肿瘤的发生、进展和恶性肿瘤都很重要。这些多能肿瘤启动细胞具有增殖和自我更新的能力，对传统的化疗和放疗具有高度的抵抗力。在这一提议中，我们假设耐药肿瘤启动细胞存在于人套细胞淋巴瘤（mcl）中，并且它们具有启动mcl形成和进展的能力。MCL是侵袭性B细胞淋巴细胞恶性肿瘤，MCL患者的中位生存期为2 - 3年。传统的化疗和放疗方案不能治愈晚期MCL。MCL的高侵袭性临床行为和低存活率使其成为鉴定和表征肿瘤起始细胞的理想模型。对启动MCL肿瘤形成的克隆源性群体进行表征，将使我们能够探索这些细胞在肿瘤发生和发展过程中的病理学。这些努力可能有助于开发新的临床前模型以及设计新的治疗策略来治疗或预防人类mcl的发病机制。

DESCRIPTION (provided by applicant): Hematological malignancies as well as many solid tumors harbor sub-populations of tumor-initiating cells that are important for tumor onset, progression, and malignancy. These multipotent tumor-initiating cells have the ability to proliferate and self-renew and are highly resistant to conventional chemotherapy and radiotherapy. In this proposal, we hypothesize that drug-resistant tumor-initiating cells exist in human mantle cell lymphoma (MCLs), and that they have the capacity to initiate the formation and progression of MCLs. MCL is aggressive B cell lymphoid malignancy and patients with MCL have median survival of two or three years. Conventional chemotherapy and radiation regimens are not curative for advanced MCL. The highly aggressive clinical behavior and low survival rates make MCL an ideal model for identification and characterization of tumor-initiating cells. Characterization of clonogenic populations that initiate MCL tumor formation will enable us to probe the pathology of these cells during tumor initiation and progression. These efforts may help the development of new preclinical models as well as the design of novel therapeutic strategies to treat or prevent the pathogenesis of MCLs in humans. PUBLIC HEALTH RELEVANCE: Non-Hodgkin's lymphomas (NHL) are the fifth most common cancer in the United States and the incidence of NHL has nearly doubled during the past three decades. However, cells initiating lymphoma have not been found. Therefore, we will use mantle cell lymphoma as a model to identify cells initiating proliferation of tumor cells and sustain tumor growth.