Characterizing Clonogenic Populations in Mantle Cell Lymphoma

描述（由申请方提供）：血液恶性肿瘤以及许多实体瘤含有肿瘤起始细胞亚群，这些细胞对肿瘤的发生、进展和恶性程度至关重要。这些多能肿瘤起始细胞具有增殖和自我更新的能力，并且对常规化疗和放疗具有高度抗性。在这个提议中，我们假设耐药肿瘤起始细胞存在于人类套细胞淋巴瘤（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细胞淋巴恶性肿瘤，MCL患者的中位生存期为2 - 3年。常规化疗和放疗方案不能治愈晚期MCL。高度侵袭性的临床行为和低存活率使MCL成为鉴定和表征肿瘤起始细胞的理想模型。启动MCL肿瘤形成的克隆形成群体的表征将使我们能够探测这些细胞在肿瘤发生和发展过程中的病理。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。 公共卫生相关性：非霍奇金淋巴瘤（NHL）是美国第五大常见癌症，在过去三十年中，NHL的发病率几乎翻了一番。然而，尚未发现起始淋巴瘤的细胞，因此，我们将使用套细胞淋巴瘤作为模型，以鉴定起始肿瘤细胞增殖的细胞并维持肿瘤生长。

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.