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SELF FUSION OF THE ALL1 GENE IN PEDIATRIC LEUKEMIA

小儿白血病中 ALL1 基因的自融合

基本信息

批准号：
2545475
负责人：
PETER K ROGAN
金额：
$ 3.87万
依托单位：
ALLEGHENY-SINGER RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-09-30 至 1999-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2545475
关键词：
acute lymphocytic leukemia adult human (21+) carcinogenesis child (0-11) chromosome translocation clinical research diagnosis design /evaluation family genetics gene mutation human subject molecular oncology neoplasm /cancer diagnosis neoplasm /cancer genetics nucleic acid hybridization pediatric neoplasm /cancer southern blotting

项目摘要

Adults and infants with acute leukemia and disruption of the ALL1 gene (at chromosome 11q23) are more likely to fail to respond to treatment or to suffer early relapse than the overall leukemia population. Although chromosome translocations that disrupt ALL1 can be recognized, submicroscopic rearrangements in this gene have been identified in individuals without cytogenetic rearrangements involving chromosome II. Both euploid and trisomy Il constitutions have been seen in this cohort of patients. in all cases studied to date, these mutations have resulted from an internal duplication of variable length (usually involving some or all of exons 2 through 8 of ALL1). It is not clear how often ALL1 mutations are missed in children. The primary purpose of this study is to retrospectively and prospectively identify mutations in children who do not have chromosome 11 translocations. By Southern hybridization with an ALL1 probe, we have identified one child with a rearrangement in this gene and mosaicism for trisomy 11 in the blast lineage. This approach may not be adequately detect disruption of ALL1 when it is present in a subset of blast cells. in this proposal, reverse-transcription followed by the polymerase chain reaction (PCR) will be used prospectively and long PCR assays will be used retrospectively to identify patients with ALL1 mutations. Following the identification of individuals with ALL1 mutations, we will determine whether one or more clinical parameters that characterize the leukemia are correlated with this genotype. Ultimately, the identification of cryptic ALL1 mutations in children with otherwise normal chromosome 11 constitutions may be useful in predicting how well they will respond to treatment or determining which treatment is most appropriate.

患有急性白血病和 ALL1 破坏的成人和婴儿基因（位于染色体 11q23）更有可能无法响应治疗或比整体白血病更早复发人口。尽管破坏 ALL1 的染色体易位可以众所周知，该基因的亚显微重排已被证实在没有细胞遗传学重排的个体中发现涉及染色体II。整倍体和 II 三体体构成在这组患者中已经看到。在所有研究的情况下迄今为止，这些突变是由内部重复引起的可变长度（通常涉及外显子 2 至 8 的部分或全部全部1)。目前尚不清楚儿童中 ALL1 突变被遗漏的频率有多少。这本研究的主要目的是回顾性和前瞻性识别没有 11 号染色体的儿童的突变易位。通过使用 ALL1 探针进行 Southern 杂交，我们已经鉴定出一名儿童的该基因发生了重排，并且急变谱系中 11 三体的镶嵌现象。这种方法可能不会当 ALL1 存在于母细胞的子集。在该提案中，逆转录随后将使用聚合酶链式反应 (PCR) 将使用前瞻性和长期 PCR 检测来回顾性地识别患有 ALL1 突变的患者。经鉴定后对于具有 ALL1 突变的个体，我们将确定是否有一个或更多表征白血病的临床参数是与该基因型相关。最终，鉴定染色体正常的儿童中的隐性 ALL1 突变 11 种宪法可能有助于预测它们的效果对治疗有反应或确定哪种治疗最有效合适的。