Characterizing Clonogenic Populations in Mantle Cell Lymphoma

描述(申请人提供)：血液系统恶性肿瘤和许多实体肿瘤都含有肿瘤起始细胞亚群，这些细胞亚群对肿瘤的发生、发展和恶性起重要作用。这些多能肿瘤启动细胞具有增殖和自我更新的能力，并且对传统的化疗和放射治疗具有高度的抵抗力。在这个方案中，我们假设在人类套细胞淋巴瘤(MCL)中存在耐药的肿瘤启动细胞，并且它们有能力启动MCL的形成和发展。MCL是一种侵袭性的B细胞淋巴系统恶性肿瘤，患者的中位生存期为两到三年。传统的化疗和放疗方案对晚期MCL不能治愈。高度侵袭性的临床行为和较低的存活率使MCL成为鉴定和鉴定肿瘤起始细胞的理想模型。对启动MCL肿瘤形成的克隆性群体的特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。 公共卫生相关性：非霍奇金淋巴瘤(NHL)是美国第五大最常见的癌症，在过去30年中，NHL的发病率几乎翻了一番。然而，尚未发现引发淋巴瘤的细胞。因此，我们将使用套细胞淋巴瘤作为模型来鉴定启动肿瘤细胞增殖和维持肿瘤生长的细胞。

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.