Somasundaram Rajesh, Prasad Mahadesh A J, Ungerbäck Jonas, Sigvardsson Mikael
Department of Clinical and Experimental Medicine, Experimental Hematopoiesis Unit, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Blood. 2015 Jul 9;126(2):144-52. doi: 10.1182/blood-2014-12-575688. Epub 2015 May 19.
B-lymphocyte development in the bone marrow is controlled by the coordinated action of transcription factors creating regulatory networks ensuring activation of the B-lymphoid program and silencing of alternative cell fates. This process is tightly connected to malignant transformation because B-lineage acute lymphoblastic leukemia cells display a pronounced block in differentiation resulting in the expansion of immature progenitor cells. Over the last few years, high-resolution analysis of genetic changes in leukemia has revealed that several key regulators of normal B-cell development, including IKZF1, TCF3, EBF1, and PAX5, are genetically altered in a large portion of the human B-lineage acute leukemias. This opens the possibility of directly linking the disrupted development as well as aberrant gene expression patterns in leukemic cells to molecular functions of defined transcription factors in normal cell differentiation. This review article focuses on the roles of transcription factors in early B-cell development and their involvement in the formation of human leukemia.
骨髓中B淋巴细胞的发育受转录因子协同作用的控制，这些转录因子形成调控网络，确保B淋巴细胞程序的激活以及其他细胞命运的沉默。这一过程与恶性转化紧密相关，因为B系急性淋巴细胞白血病细胞在分化过程中表现出明显的阻滞，导致未成熟祖细胞的扩增。在过去几年中，对白血病基因变化的高分辨率分析表明，正常B细胞发育的几个关键调节因子，包括IKZF1、TCF3、EBF1和PAX5，在很大一部分人类B系急性白血病中发生了基因改变。这为将白血病细胞中发育受阻以及异常基因表达模式与正常细胞分化中特定转录因子的分子功能直接联系起来提供了可能性。这篇综述文章重点关注转录因子在早期B细胞发育中的作用及其在人类白血病形成中的参与情况。
