Molecular determinants of prognosis in limited-stage follicular lymphoma

局限性滤泡性淋巴瘤预后的分子决定因素

• 批准号: 9095261
• 负责人: ABNER LOUISSAINT
• 金额: $ 14.03万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-04 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9095261
• 关键词: Adult; Advisory Committees; Algorithms; Antigens; Autoimmunity; BCL2 gene; Basic Science; Behavior; Biological; Biology; Chairperson; Child; Childhood; Classification; Clinical; Clinical Investigator; Clinical Research; DNA Sequence Alteration; Data; Development; Diagnosis; Disease; Excision; Faculty; Follicular Lymphoma; Foundations; Funding; Gene Chips; Gene Expression; Gene Expression Profile; Gene-Modified; Genes; Goals; Health; Hematopathology; Histones; Histopathologic Grade; Immunoglobulin Somatic Hypermutation; Infection; Infertility; Investigation; Limited Stage; Lymphoma; Lymphomagenesis; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Molecular; Molecular Profiling; Mutate; Mutation; Nature; Non-Malignant; North America; Oncologist; Operative Surgical Procedures; Outcome; Pathogenesis; Pathologic; Pathologist; Pathology; Patients; Phenotype; Play; Radiation; Recurrence; Relapse; Research; Research Personnel; Resources; Rest; Role; Second Primary Cancers; Solid; Staging; Structure of germinal center of lymph node; Subgroup; Technology; Testing; Therapeutic; Time; Toxic effect; Training; Variant; Work; activation-induced cytidine deaminase; base; career; chemotherapy; clinical material; cohort; comparative genomic hybridization; conventional therapy; deep sequencing; exome sequencing; experience; improved; innovation; mRNA Expression; novel; outcome forecast; patient oriented; patient oriented research; prognostic; prognostic tool; programs; protein expression; rare variant; skills; tool; Adult; Advisory Committees; Algorithms; Antigens; Autoimmunity; BCL2 gene; Basic Science; Behavior; Biological; Biology; Chairperson; Child; Childhood; Classification; Clinical; Clinical Investigator; Clinical Research; DNA Sequence Alteration; Data; Development; Diagnosis; Disease; Excision; Faculty; Follicular Lymphoma; Foundations; Funding; Gene Chips; Gene Expression; Gene Expression Profile; Gene-Modified; Genes; Goals; Health; Hematopathology; Histones; Histopathologic Grade; Immunoglobulin Somatic Hypermutation; Infection; Infertility; Investigation; Limited Stage; Lymphoma; Lymphomagenesis; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Molecular; Molecular Profiling; Mutate; Mutation; Nature; Non-Malignant; North America; Oncologist; Operative Surgical Procedures; Outcome; Pathogenesis; Pathologic; Pathologist; Pathology; Patients; Phenotype; Play; Radiation; Recurrence; Relapse; Research; Research Personnel; Resources; Rest; Role; Second Primary Cancers; Solid; Staging; Structure of germinal center of lymph node; Subgroup; Technology; Testing; Therapeutic; Time; Toxic effect; Training; Variant; Work; activation-induced cytidine deaminase; base; career; chemotherapy; clinical material; cohort; comparative genomic hybridization; conventional therapy; deep sequencing; exome sequencing; experience; improved; innovation; mRNA Expression; novel; outcome forecast; patient oriented; patient oriented research; prognostic; prognostic tool; programs; protein expression; rare variant; skills; tool

DESCRIPTION (provided by applicant): The research objective of this proposal is to define the molecular distinctions between prognostically distinct subsets of limited-stage FL, in order to improve therapeutic algorithms. Irrespective of the therapeutic approach, approximately 60% of cases remain localized and never progress, while the remainder of cases ultimately progress to more aggressive lymphoma. Currently, oncologists have no way of distinguishing the cases that will ultimately progress from those that will remain localized. Nevertheless, 40% of these patients are treated with aggressive chemotherapy on the basis of imprecise algorithms despite the toxicities associated with this treatment. Thus, there is a critical need to obtain more accurate indicators of outcome on which to base therapeutic decisions. We aim to define the molecular alterations that may distinguish two subgroups of FL that we believe are prognostically and biologically distinct. The results of this proposal will significantly impact lymphoma management, as it would identify a cohort of patients may potentially be spared the toxic effects of radiation and/or aggressive chemotherapy. My overall goal for this training period is to become an independently funded clinical investigator with an innovative clinical research program in patient-oriented lymphoma research. Over the past two years since joining the MGH Pathology faculty, I have received tremendous support from my chairman, Dr. Louis, in my effort to work towards my career and research objectives. Completion of the studies proposed will provide the substrate for me to develop the appropriate skills necessary for me to achieve this goal with the mentorship of Dr. Shiv Pillai and Dr. Nancy Harris and the rest of my advisory committee. Dr. Pillai is internationally known for his expertise in the biology of autoimmunity and lymphomagenesis. He is also famous for the quality of his mentorship. We have collaborated on the identification of novel mutations in adult FL using deep sequencing technology. Dr. Harris is one of the most distinguished experts in lymphoma diagnosis, classification and investigation, with worldwide recognition by both pathologists and lymphoma oncologists. Together with the rest of my advisory team, Dr. Pillai and Dr. Harris will provide the perfect blend of mentorship to guide my development to an independent investigator specifically in patient-oriented lymphoma research. I anticipate that the results obtained from the proposed studies will enhance our understanding of FL biology, while forming a solid foundation on which to launch my career as a clinical investigator. I believe that with my background in basic and clinical research, my experience in clinical hematopathology, combined with the clinical material, resources and network of expert clinical and research mentors currently available to me at MGH, the K23 award would make me uniquely situated to accomplish my career and research objectives.

描述（由申请人提供）：该提案的研究目标是定义有限阶段FL的预后不同子集之间的分子区别，以便为了 改善治疗算法。不管治疗方法如何，大约60％的病例仍在定位并且永远不会进行，而其余病例最终会发展为更具侵略性的淋巴瘤。目前，肿瘤学家无法区分最终将进展的案例与将要定位的案例。然而，尽管与这种疗法有关的毒性，但这些患者中有40％的患者接受了侵略性化疗的治疗。因此，迫切需要获得更准确的结果指标，以基于治疗性决策。我们的目的是定义可能区分两个我们认为在预后和生物学上截然不同的FL亚组的分子变化。该提案的结果将显着影响淋巴瘤的管理，因为它将确定一系列患者可能会免除放射线和/或侵略性化疗的毒性作用。我在这个训练期的总体目标 将成为由患者淋巴瘤研究的创新临床研究计划的独立临床研究者。自加入MGH病理学院以来，过去两年中，我得到了董事长Louis博士的巨大支持，以努力朝着自己的职业和研究目标努力。提议的研究的完成将为我提供基础，以通过Shiv Pillai博士和Nancy Harris博士以及我的其余咨询委员会的指导来开发我实现这一目标所必需的适当技能。 Pillai博士以其自身免疫生物学的专业知识而闻名 淋巴作用。他还以指导的质量而闻名。 We have collaborated on the identification of novel mutations in adult FL using deep sequencing technology.哈里斯博士是淋巴瘤诊断，分类和研究最杰出的专家之一，病理学家和淋巴瘤肿瘤学家都认可了全球。 Pillai博士和Harris博士将与我的其他咨询团队一起提供完美的指导融合 指导我的发展对专门针对患者淋巴瘤研究的独立研究者。我预计从拟议的研究中获得的结果将增强我们对FL生物学的理解，同时构成扎实的基础，以启动我作为临床研究者的职业。我相信，借助我在基础和临床研究方面的背景，我在临床血症病理学方面的经验以及我目前可在MGH上可以使用的临床材料，资源和专家临床和研究导师网络，K23 Award将使我独一无二地实现自己的职业生涯和研究目标。