Biochemistry of Leukemia Virus Core Binding Factor

超出所提供的空间。runx1 - cbfi_是胚胎中造血干细胞出现所需的异二聚体转录因子。在出生后的生命中，造血干细胞或承诺祖细胞中的RUNXl和CBFB基因突变有助于人类白血病的形成。RUNX1 （AML1）基因被大约12种不同的染色体易位破坏，包括急性髓细胞白血病和儿童淋巴细胞白血病中的t（8;21）、t（12;21）和t(3;21)，以及治疗相关的白血病和骨髓增生异常。CBFB基因在急性髓性白血病中被inv重排（16）。总的来说，RUNX1和CBFB基因在大约四分之一的急性髓细胞和淋巴细胞白血病中重排。在这里，我们建议研究在小鼠正常造血发育过程中对Runxl-CBFI_异源二聚体的需求。我们将确定Runxl-CBF_在特化的“造血内皮”中的功能对于产生第一批造血干细胞是否必要和充分。我们将通过描述胚胎中调节Runxl表达的顺式作用序列来开始识别指定第一批造血干细胞的信号。最后，我们将探讨在出生后造血后期对Runxl-CBFI_功能的持续需求。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. Runxl-CBFI_ is a heterodimeric transcription factor required for the emergence of hematopoietic stem cells in the embryo. During postnatal life mutations in the RUNXl and CBFB genes in a hematopoietic stem cell or committed progenitor contributes to the formation of human leukemias. The RUNX1 (AML1) gene is disrupted by about a dozen different chromosomal translocations, including the t(8;21 ), t(12;21), and t(3;21) in acute myeloid and pediatric lymphoblastic leukemias, and in therapy related leukemias and myelodysplasias, respectively. The CBFB gene is rearranged in acute myeloid leukemias by the inv(16). Together, the RUNX1 and CBFB genes are rearranged in approximately one quarter of all acute myeloid and lymphoblastic leukemias. Here we propose to examine the requirement for the Runxl-CBFI_ heterodimer throughout normal hematopoietic development in mice. We will determine whether Runxl-CBF_ function in a specialized "hemogenic endothelium" is necessary and sufficient in order to produce the first hematopoietic stem cells. We will begin to identify the signals that specify the first hematopoietic stem cells by characterizing the cis- acting sequences that regulate Runxl expression in the embryo. Finally we will examine the requirement for continued Runxl-CBFI_ function during later stages of postnatal hematopoiesis. PERFORMANCE SITE ========================================Section End===========================================