ETIOLOGY OF TREATMENT INDUCED SECONDARY LEUKEMIA

该项目的重点是分析机制 导致患者发生治疗相关急性髓细胞白血病（t-AML） 既往接受过多种化疗药物和/或 辐射 最初，我们专注于绘制基因的长区域， 染色体5（5 q），因为5 q的缺失是最常见的 烷化剂治疗后t-AML异常和/或 辐射，我们将5 q31上的2到4兆碱基段定义为 关键区域。 7号染色体的丢失是t- AML;我们已经定位了7 q上的两个位点（7 q22和7 q32 -33）， 关键基因 我们将定义染色体上的关键区域 5和7更精确，并寻找相关基因。 的药物 靶向拓扑异构酶II有时在t-AML中与平衡 易位，特别是涉及MLL基因在11 q23。 我们 分析MLL的结构和MLL基因组序列， 断点，以寻找潜在的断裂机制， MLL易位后暴露于表鬼臼毒素。 我们 将分析细胞定位，磷酸化状态和 最常见的MLL伴侣基因（即AF 4）的结合潜力 （4q21）。

The focus of this program project has been the analysis of mechanisms leading to therapy-related acute myeloid leukemia (t-AML) in patients who previously received a variety of chemotherapeutic agents and/or radiation. Initially we focussed on mapping genes on the long are of chromosome 5 (5q) because deletions of 5q are one of the most common abnormalities in t-AML following treatment with alkylating agents and/or radiation and we defined a 2 to 4 mega base segment on 5q31 as the critical region. Loss of chromosome 7 is the most common change in t- AML; we have mapped two loci on 7q (7q22 and 7q32-33) as containing the critical genes. We will define the critical regions on chromosomes 5 and 7 more precisely and search for the involved genes. Drugs that target topoisomerase II are sometime associated in t-AML with balanced translocations especially involving the MLL gene at 11q23. We are analyzing the structure of MLL and the sequence of the MLL genomic breakpoints to search for potential mechanisms for breakage and translocation of MLL following exposure to the epipodophyllotoxins. We will analyze the cellular localization, phosphorylation state and the binding potential of the most common MLL partner gene, namely AF4 (4q21).