Impact of primary tumor development stage on prognosis and outcome in B-ALL

原发肿瘤发展阶段对 B-ALL 预后和结果的影响

• 批准号: 8754687
• 负责人: Christopher S Carlson
• 金额: $ 22.97万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8754687
• 关键词: Acute Lymphocytic Leukemia; Affect; Agammaglobulinaemia tyrosine kinase; Alleles; B cell differentiation; B-Cell Acute Lymphoblastic Leukemia; B-Cell Lymphomas; B-Lymphocytes; Biological; Biology; Blast Cell; Categories; Cell Culture Techniques; Cell Lineage; Cells; Child; Chromosomes; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 14; DNA Sequence Rearrangement; Data; Derivation procedure; Development; Diploidy; Elderly; Event; Exclusion; Frequencies; Genetic Recombination; Haploidy; Hematopoietic stem cells; IGH@ gene cluster; Immunoglobulins; Karyotype; Laboratories; Libraries; Light; Malignant Childhood Neoplasm; Malignant Neoplasms; Mature B-Lymphocyte; Measurement; Measures; Methods; Molecular Profiling; Outcome; Pathway interactions; Patients; Pharmaceutical Preparations; Primary Neoplasm; Protein Tyrosine Kinase; Publishing; Reporting; Research; SYK gene; Sampling; Signal Transduction; Staging; Stem cell transplant; Subgroup; Testing; Therapeutic; Transplant Recipients; Treatment Protocols; Tumor Subtype; Tumor-Derived; Ursidae Family; V(D)J Recombination; base; cell type; differentiated B cell; effective therapy; inhibitor/antagonist; neoplastic cell; novel therapeutic intervention; outcome forecast; pre-B cell receptor; prognostic; public health relevance; research study; response; standard care; therapy development; tool; tumor

DESCRIPTION (provided by applicant): B-cell Acute Lymphocytic Leukemia (B-ALL) is the most common cancer in children. While great progress has been made in the development of treatments for B-ALL, approximately 20% of patients still fail to respond to standard therapies. Thus, studies that enhance our understanding of the basic biology behind these aggressive sub-types of B-ALL remain important; as such research could plausibly identify effective therapies for patients who have failed standard treatment. The present proposal is based on the observation that a specific sub-type of aggressive B-ALL ("low hypodiploid B-ALL") may be derived from very primitive precursors of B-cells. The first two aims proposed will test the hypothesis that these tumors not only derive from primitive precursors, but also retain the activity of specific biological pathways expressed in this cell type, specifically responsiveness t signals from the pre-B cell receptor. If so, then drugs recently developed for mature B cell lymphomas (which typically affect the elderly) may be applicable in this small subset of B-ALL. Thus, the third aim of the proposal is to develop laboratory methods by which to test whether these tumors are especially sensitive to the drug class in question (fostamatinib and ibrutinib).

描述（由申请人提供）：B 细胞急性淋巴细胞白血病 (B-ALL) 是儿童中最常见的癌症。尽管 B-ALL 治疗方法的开发取得了巨大进展，但大约 20% 的患者仍然对标准疗法没有反应。因此，加强我们对这些侵袭性 B-ALL 亚型背后的基础生物学的理解的研究仍然很重要。因为此类研究可以为标准治疗失败的患者找到有效的治疗方法。本提议基于以下观察：侵袭性 B-ALL 的特定亚型（“低亚二倍体 B-ALL”）可能源自 B 细胞的非常原始的前体。提出的前两个目标将检验以下假设：这些肿瘤不仅源自原始前体，而且保留了该细胞类型中表达的特定生物途径的活性，特别是来自前 B 细胞受体的信号反应性。如果是这样，那么最近开发的针对成熟 B 细胞淋巴瘤（通常影响老年人）的药物可能适用于这一小部分 B-ALL。因此，该提案的第三个目标是开发实验室方法来测试这些肿瘤是否对所讨论的药物类别（福斯塔替尼和伊布替尼）特别敏感。