Biochemistry of Leukemia Virus Core Binding Factor

Runx1-CBFI_1是一种异二聚体转录因子，是造血干细胞出现所必需的 在胚胎中。在出生后生命中，造血干细胞中RUNX1和Cbfb基因的突变 或忠诚的祖细胞有助于人类白血病的形成。RUNX1(AML1)基因是 被十几种不同的染色体易位破坏，包括t(8；21)，t(12；21)和t(3；21) 在急性髓系白血病和儿童淋巴母细胞白血病中，以及在治疗相关白血病和 分别为骨髓发育不良。Cbfb基因在急性髓系白血病中由inv(16)重排。 RUNX1和Cbfb基因加在一起，在大约四分之一的急性髓系细胞中发生重排 和淋巴细胞性白血病。 在这里，我们建议检查在整个正常情况下对Runx1-CbFI_异二聚体的要求 小鼠的造血发育。我们将确定Runxl-cbf_函数是否在专门的 “血源性内皮”是产生第一个造血干细胞的必要条件和充分条件。 我们将通过鉴定顺式造血干细胞的特征来开始鉴定第一批造血干细胞的信号。 调节胚胎中Runx1表达的作用序列。最后，我们将研究以下要求 在出生后造血的后期持续Runxl-CBFI_Function。

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.