Biochemistry of Leukemia Virus Core Binding Factor

Runxl-CBFI_是造血干细胞出现所需的异二聚体转录因子 在胚胎中。在出生后生命期间，造血干细胞中RUNX 1和CBFB基因的突变 或定向祖细胞有助于人类白血病的形成。RUNX 1（AML 1）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） 在急性骨髓性和小儿淋巴母细胞性白血病中，以及在治疗相关的白血病中， 骨髓增生异常。CBFB基因在急性髓性白血病中通过inv重排（16）。 总之，RUNX 1和CBFB基因在大约四分之一的急性髓系白血病中重排。 和淋巴母细胞白血病。 在这里，我们建议检查在正常的免疫反应中Runxl-CBFI_异二聚体的需求。 小鼠造血发育。我们将确定Runxl-CBF_ function是否在专门的 为了产生第一个造血干细胞，“造血内皮”是必要的和足够的。 我们将开始通过表征顺式- 调节Runxl在胚胎中表达的作用序列。最后，我们将研究以下要求： 在出生后造血的后期阶段持续Runxl-CBFI_功能。

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.