Defining the biology of HIV-associated aggressive B-cell lymphoma in Southern Africa

南部非洲 HIV 相关侵袭性 B 细胞淋巴瘤的生物学定义

• 批准号: 10296755
• 负责人: Katherine Antel
• 金额: $ 11.05万
• 依托单位: UNIVERSITY OF CAPE TOWN
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-27 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10296755
• 关键词: Advanced Development; Africa; Africa South of the Sahara; African; Algorithms; Antigens; Area; Award; B-Cell Activation; B-Cell Lymphomas; B-Lymphocytes; BRAF gene; Bioinformatics; Biological; Biological Markers; Biological Models; Biology; Biometry; Caucasians; Characteristics; Chronic; Classification; Clinical; Clinical Trials; Country; DNA Sequence Alteration; Dana-Farber Cancer Institute; Data Set; Development Plans; Diagnosis; Diagnostic; Diffuse Pattern; Doctor of Philosophy; Ensure; Europe; Feasibility Studies; Future; Gene Expression; Gene Expression Profile; Gene Mutation; Genetic; Genetic Heterogeneity; Genetic Transcription; Genetic study; Genomics; Goals; HIV; HIV Infections; HIV Seronegativity; HIV Seropositivity; Health Priorities; Hematologist; Hepatitis B; Hepatitis C virus; Heterogeneity; High Prevalence; Hospitals; Human Herpesvirus 4; Immunosuppression; Income; Individual; International; Laboratories; Lymphoma; Malignant Neoplasms; Mediating; Mentors; Mentorship; Morbidity - disease rate; Mutation; Non-Hodgkin' s Lymphoma; Oncogenic; Outcome; Pathogenesis; Pathogenicity; Pathologic; Pathway interactions; Patient-Focused Outcomes; Patients; Persons; Physicians; Play; Population; Positioning Attribute; Recurrence; Research; Research Design; Risk; Role; Scientist; South Africa; South African; Southern Africa; Structure; Structure of germinal center of lymph node; Taxonomy; Therapeutic; Time; Training Programs; Translating; Tuberculosis; Universities; Virus Diseases; Work; base; biomarker-driven; career; career development; co-infection; comorbidity; cost; cost effective; genomic aberrations; high risk; improved outcome; in vivo; inhibitor/antagonist; innovation; large cell Diffuse non-Hodgkin' s lymphoma; medical schools; molecular diagnostics; mortality; next generation sequencing; novel; novel diagnostics; programs; skills; survival outcome; targeted treatment; training opportunity; treatment response; treatment stratification; tumorigenesis

PROJECT SUMMARY ABSTRACT Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma, also among people with HIV, and accounts for roughly one-third of all non-Hodgkin lymphoma (NHL) cases worldwide. The 2008 classification of DLBCL recognized germinal centre B-cell (GCB) and activated B-cell (ABC)/non-GCB subtypes, and also a group that was unclassifiable based on gene expression. More recently, two research groups have independently identified subtypes of DLBCL based on shared genomic aberrations. In both studies, these subtypes differ in respect to pathogenic mechanisms, clinical characteristics, and survival outcomes. Although these studies represent significant advances in our understanding of DLBCL from the US and Europe, there is much work still to be done in describing the genetic patterns of DLBCL in sub-Saharan Africa, especially in patients with HIV. Further understanding of genetic and transcriptional heterogeneity of these lymphomas could inform new diagnostic and treatment approaches that improve outcomes for patients. The scientific goal of this proposal is to establish a biologically informed taxonomy of HIV-associated DLBCL in South Africa. The specific aims are to: (1) Establish genetically and transcriptionally defined subtypes of HIV-associated DLBCL in South Africa; and (2) Establish clinicopathological features of HIV-associated DLBCL associated with these subsets. This proposal is responsive to areas of critical need in South Africa: research that is highly relevant to regional health priorities; and the career development of a local clinician-scientist. These studies also support the long-term goal of developing low-cost diagnostic strategies that guide the treatment of lymphoma in South Africa. The project PI, Dr Katherine Antel, is a clinical hematologist at the University of Cape Town with the career goal of independently conducting research that will improve outcomes for patients with lymphoma. Her PhD work showed that in South Africa there are numerous local obstacles to lymphoma diagnosis and, notably, that within this tuberculosis (TB)- endemic area, patients with lymphoma are at high risk of misdiagnosis with extrapulmonary TB. The diagnostic algorithm developed as part of her research has led to a shorter time-to-diagnosis of lymphoma at Groote Schuur Hospital. A comprehensive career development plan comprising structured activities and mentorship opportunities will enable Dr Antel to continue her career development as a physician-scientist by acquiring advanced skills in 1) next-generation sequencing; 2) bioinformatics; 3) biostatistical approaches for integrating genomics and clinical datasets; and 4) cellular and in vivo approaches to interrogate the effects of novel gene mutations. This K43 award will position her to build an independent program of research in lymphoma that drives innovative diagnostic and therapeutic approaches for patients in southern Africa.

项目摘要