DETECTION OF SOMATIC GENE MUTATIONS IN HEMATOLOGIC DISEASES

血液疾病中体细胞基因突变的检测

• 批准号: 5201208
• 负责人: S ROSENFELD
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5201208
• 关键词: DNA; acute myelogenous leukemia; biopsy; bone marrow disorder; chromosome disorders; chronic myelogenous leukemia; family genetics; fusion gene; gene mutation; genetic disorder; hematopoietic stem cells; human genetic material tag; human subject; interview; leukocyte count; loss of heterozygosity; lymphocyte; monocyte; retinoid binding proteins; skin

A number of hematologic diseases have been shown to result from clonal expansion of an abnormal stem cell. In a few cases, typically associated with macroscopic chromosomal structural abnormalities, individual genes have been implicated. Examples include chronic myelogenous leukemia (CML) and the BCR-Abl fusion gene, and acute promyelocytic leukemia (APL) and the retinoic acid receptor. Detection of a specific genetic abnormality has had significant impact on the diagnosis (CML and APL) and treatment (APL) of these disorders. No specific or consistent genetic abnormality has been detected in the majority of clonal bone marrow disorders, including the myelodysplastic syndrome and the myeloproliferative syndromes other than CML. We are using the technique of representation difference analysis (RDA) to look for changes in the somatic DNA of individuals with clonai bone marrow disorders. Abnormal DNA is collected by isolating peripheral blood or bone marrow mononuclear cells. Unaffected DNA used to drive the kinetic enrichment of the abnormal gene can be obtained from several sources. In rare cases, blood or bone marrow specimens are available both before and after the evolution of the disease. In this case, the earlier specimen can serve as the "driver", or normal, and the latter as the "target", or abnormal. In the case of a mutation associated with homozygous loss of genetic material, this order can be reversed. Most patients will not have pre-evolution samples available. In these cases driver DNA can be obtained from a pool of peripheral blood mononuclear cells from the patient's parents (if available) or from skin obtained from the affected individual by bunch biopsy.

许多血液病已被证明是由于克隆性 异常干细胞的扩增。在某些情况下，通常与 肉眼可见的染色体结构异常， 被牵连了慢性粒细胞白血病（CML） 和BCR-Abl融合基因，以及急性早幼粒细胞白血病（APL）和 视黄酸受体检测特定的遗传异常 对诊断（CML和APL）和治疗有重大影响 (APL)这些疾病。没有特定或一致的遗传异常 在大多数克隆性骨髓疾病中检测到， 包括骨髓增生异常综合征和骨髓增生异常综合征 CML以外的症状 我们正在使用代表性差异分析（RDA）技术， 寻找克隆性骨髓炎患者体细胞DNA的变化 紊乱通过分离外周血或骨骼收集异常DNA 骨髓单个核细胞未受影响的DNA用于驱动动力学 异常基因的富集可以从多种来源获得。在 罕见的情况下，血液或骨髓样本可在之前和之后获得。 在疾病的演变之后。在这种情况下，早期的标本可以 作为“驱动程序”，或正常，后者作为“目标”，或 不正常.在与纯合缺失相关的突变的情况下， 遗传物质，这个顺序可以颠倒。大多数患者不会有 进化前的样本在这些情况下，可以获得驱动DNA 从患者的外周血单核细胞池中， 父母（如果有的话）或从受影响的个人获得的皮肤 进行活检