DETECTION OF SOMATIC GENE MUTATIONS IN HEMATOLOGIC DISEASES

许多血液病已被证明是由克隆引起的。 异常干细胞的扩增。在少数情况下，通常与 有宏观的染色体结构异常，个别基因 都有牵连。例如慢性粒细胞白血病(CML) 和bcr-Abl融合基因，与急性早幼粒细胞白血病(APL)和 维甲酸受体。检测特定的遗传异常 对诊断(CML和APL)和治疗产生了重大影响 (APL)。没有特定或一致的基因异常 在大多数克隆性骨髓疾病中都被检测到， 包括骨髓增生异常综合征和骨髓增生性疾病 慢性粒细胞白血病以外的其他症状。 我们正在使用表示差异分析(RDA)技术来 寻找克隆性骨髓患者体细胞DNA的变化 精神错乱。异常DNA是通过分离外周血或骨骼来收集的 骨髓单个核细胞。未受影响的DNA用于驱动动力学 异常基因的浓缩可以从几个来源获得。在……里面 极少数情况下，血液或骨髓样本既有以前的也有 在疾病进化之后。在这种情况下，较早的样本可以 充当“司机”，或正常，而后者作为“目标”，或 不正常。在与纯合子缺失相关的突变的情况下 遗传物质，这个顺序是可以颠倒的。大多数患者都不会有 提供进化前样本。在这些情况下，可以获得司机DNA 从病人的外周血单核细胞池中提取 父母(如果有的话)或从受影响个人获得的皮肤 通过束状活检。

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.