Project 03: Leukemia Research (LR)

项目摘要-白血病研究(LR) 俄亥俄州立大学综合癌症中心的白血病研究(LR)计划， 由医学博士约翰·C·伯德和医学博士拉米罗·加尔松领导，有来自7个系和4个学院的57名成员 (工程学、药学、医学和兽医)。LR计划仍然专注于病因学， 白血病的发病机制、预后和治疗，重点介绍急性髓系白血病、慢性粒细胞白血病 淋巴细胞白血病(CLL)、毛细胞白血病(HCL)和成人T细胞白血病(ATL)。LR已经展示了 在将临床前发现转化为临床试验并最终转化为临床试验的能力方面具有独特的优势 申请。在LR计划中，考虑到基础、临床前、转换和临床的广度，我们将专注于 关于以下两个具体目标：1)探索和整合遗传的、表观遗传的、非编码的RNA，以及 白血病细胞的免疫抑制特征，以加强危险分层和靶点识别；2) 促进表观遗传学、靶向疗法和免疫疗法在临床前和临床上的发展 白血病转化的原因、进展和最终的重点是治疗这些疾病。LR计划 成员在2014年1月12日至19年11月30日期间发表了702篇与癌症相关的手稿。其中33%是内部 程序性(来自LR计划的多名作者)，23%是跨程序的(来自多名作者 OSUCCC计划)，77%是多机构的(来自LR和其他机构的作者)。总数 合作出版占88%。LR计划的资金总额为1170万美元，以癌症为重点 资金，其中630万美元是同行审查，包括来自NIH的510万美元直接资金(来自NCI的490万美元)。超过了 在过去的5年里，LR计划成员累计参加了8835名试验；1582名参加了干预性试验 (包括1,556项治疗性试验)和7,253项非干预试验。未来计划包括：1)增强 进一步提高我们发现和翻译工作的质量；2)进一步剖析 可能重新定义AML和CLL的分类和治疗方式 以精确医学为基础的方法；3)整合患者友好、靶向和免疫疗法，以 开发根治方法；以及4)集中招聘中层资助的调查人员 补充LR计划和伯洛托尼亚免疫研究所的专门研究领域- 肿瘤学。总体而言，我们的计划致力于支持开发一种无化疗的方法来 治疗白血病。因此，这种策略将优先于传统的化疗方法，通过 早期的研究人员与BEAT AML和联盟财团一起发起了试验。通过类似的路径，一个 将启动MDS试验(停止MDS™)，并将重点放在一个未得到满足的需求领域。最后，我们的节目将 支持提交方案赠款，如孢子和P01，使我们能够实现我们的 战略研究目标。这将通过提供试点资金和协调共享资源来实现 将为这类应用提供便利。

PROJECT SUMMARY – LEUKEMIA RESEARCH (LR) The Leukemia Research (LR) Program at The Ohio State University Comprehensive Cancer Center (OSUCCC), led by John C. Byrd, MD, and Ramiro Garzon, MD, has 57 members from 7 Departments and 4 Colleges (Engineering, Pharmacy, Medicine, and Veterinary Medicine). The LR Program remains focused on the etiology, pathogenesis, prognosis, and treatment of leukemia, with emphases on acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL) and adult T-cell leukemia (ATL). LR has demonstrated unique strengths in its ability to translate preclinical findings to clinical testing, and ultimately to clinical application. Given the breadth of basic, preclinical, translational and clinical, within the LR Program, we will focus on the following two specific aims: 1) To Explore and integrate genetic, epigenetic, non-coding RNAs, and immunosuppressive features of leukemic cells in order to enhance risk stratification and target identification; 2) To foster preclinical and clinical development of epigenetic, targeted, and immunologic therapeutics directed at the causes of leukemic transformation, its progression and ultimate focus on curing these diseases. LR Program members published 702 cancer-relevant manuscripts between 12/01/14 and 11/30/19. Of these, 33% were intra- programmatic (multiple authors from LR Program), 23% were inter-programmatic (authors from multiple OSUCCC Programs), and 77% were multi-institutional (authors from both LR and another institution). The total collaborative publications is 88%. LR Program funding stands at $11.7M in overall direct, cancer-focused funding, of which $6.3M is peer-reviewed, including $5.1M direct funding from NIH ($4.9M from NCI). Over the last 5 years, LR Program members have accrued 8,835 participants to trials; 1,582 to interventional trials (including 1,556 therapeutic trials) and 7,253 to non-interventional trials. Future plans include: 1) enhancement of collaborative science to further improve the quality of our discovery and translational work; 2) further dissection of the genetic subtypes of leukemia to potentially re-define how AML and CLL are classified and treated using precision medicine-based approaches; 3) integration of patient-friendly, targeted and immune therapies to develop curative treatment approaches; and 4) focused recruiting of mid-level funded investigators with dedicated research areas that complement the LR Program and also the Pelotonia Institute for Immuno- Oncology. Overall, our program is committed to support the development of a chemotherapy-free approach to treat leukemia. Therefore, this strategy will be prioritized over conventional chemotherapy approaches through early investigator initiated trials along with the BEAT AML and the Alliance consortia. Through a similar path, an MDS trial (Stop MDS™) will be been initiated and will focus on an area of unmet need. Last, our program will support the submission of programmatic grants such as SPORE and P01 that will allow us to achieve our strategic research goals. This will be achieved by providing pilot funding and coordinating shared resources that will facilitate such applications.