Hematologic Malignancies

项目摘要 血液学恶性肿瘤（HM）计划的目标是更好地了解生物学 潜在的血液肿瘤，并应用这些知识，以提高诊断和治疗这些 紊乱为了实现这一目标，我们有一个广泛的研究计划，主要主题是 疾病发病机制、生物标志物监测和新疗法的开发。内的41名成员 我们的计划代表7个部门内的医学院和化学系在 人文科学学院。他们得到了同行评审研究的支持，总额为860万美元，包括 9辆R 01。同行评审的资金包括来自NCI的430万美元，来自其他NIH研究所的270万美元，以及来自 其他来源我们的计划强调在诊断和新的临床转化研究 从临床到实验室，在患者来源的组织的研究中。在此CCSG循环期间， 在同行评审期刊上发表了670篇出版物，其中23%为方案内出版物，36%为 其中94%是跨学科的，32%是在高影响力的期刊上发表的（32% IF >10; 17% 如果>20）。在上一个资助期间，我们的成员担任临床试验的主要研究者， 几个FDA批准，包括用于慢性移植物抗宿主病的伊曲替尼和mogamulizumab， 维布妥昔单抗治疗皮肤T细胞淋巴瘤。我们的计划成员一直是主要贡献者， 开发用于血液系统恶性肿瘤的抗CD 47抗体magrolimab，目前正在进行 急性髓细胞白血病和骨髓增生异常综合征临床试验的参与者。协作组 慢性淋巴细胞白血病的临床试验，包括联合伊替尼和维奈托克，已经由 节目成员。血液肿瘤项目成员开创了测量液体 活检的预后和跟踪弥漫性大B细胞淋巴瘤与潜在的实践改变的结果。 我们的临床前和实验室研究推进了新的免疫治疗方法，包括原位免疫治疗。 疫苗接种和mRNA治疗剂的体内递送，在某些情况下已经进入早期临床试验。 正在进行的基础科学工作的重点是白血病干细胞的特征，应用单- 细胞技术用于疾病和细胞异质性的研究， 关注Myc癌基因、表观遗传对血液恶性肿瘤的贡献以及免疫系统的作用。 系统来对抗这些癌症。今后，我们的目标是继续努力， 用更安全、更有效的血液肿瘤疗法取代目前的细胞毒性疗法。

PROJECT SUMMARY The goal of the Hematologic Malignancies (HM) Program is to gain a better understanding of the biology underlying hematologic neoplasms and to apply this knowledge to improve the diagnosis and treatment of these disorders. In working toward this goal, we have a broad research program with major themes of mechanisms of disease pathogenesis, biomarker monitoring, and the development of new therapies. The 41 members within our program represent 7 departments within the School of Medicine and the Department of Chemistry in the School of Humanities and Sciences. They are supported by peer-reviewed research totaling $8.6M, including 9 R01s. Peer-reviewed funding consists of $4.3M from the NCI, $2.7M from other NIH institutes, and $1.6M from other sources. Our program has emphasized translational research to the clinic in diagnostics and novel therapeutics and from the clinic to the laboratory in studies of patient-derived tissues. During this CCSG cycle, 670 publications have been published in peer-reviewed journals, of which 23% were intra-programmatic, 36% were inter-programmatic, 94% were multi-institutional, and 32% were in high-impact journals (32% IF >10; 17% IF >20). During the last funding period, our members served as lead investigators for clinical trials leading to several FDA approvals, including ibrutinib for chronic graft vs. host disease and mogamulizumab and brentuximab for cutaneous T cell lymphoma. Our program members have been major contributors to the development of the anti-CD47 antibody magrolimab for hematologic malignancies and are now active participants in clinical trials for acute myeloid leukemia and myelodysplastic syndromes. Cooperative group clinical trials in chronic lymphocytic leukemia, including combination ibrutinib and venetoclax, have been led by program members. Hematologic Malignancies program members have pioneered the measurement of liquid biopsies for prognosis and tracking of diffuse large B cell lymphoma with potentially practice-changing results. Our pre-clinical and laboratory studies have advanced novel immunotherapy methods, including in situ vaccination and in vivo delivery of mRNA therapeutics that have entered early-phase clinical trials in some cases. Ongoing basic science efforts are focused on the characterization of leukemia stem cells, application of single- cell technologies to the study of disease and cellular heterogeneity, investigations into lymphomagenesis with attention to the Myc oncogene, epigenetic contributions to hematologic malignancies, and the role of the immune system in combatting these cancers. In the future, we aim to continue our efforts to develop approaches to replace current cytotoxic regimens with safer, more effective therapies for hematologic neoplasms.