Liebermann D A, Hoffman-Liebermann B
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
Curr Opin Hematol. 1994 Jan;1(1):24-32.
A great body of evidence indicates that hematopoietic cytokines and the availability of their cognate receptors at the cell membrane surface of myeloid progenitors play crucial roles in lineage commitment and differentiation. Little is known of how these receptors couple to downstream signal transduction pathways to convert the extracellular signal into a change in the genetic program. Lineage switching of myeloid progenitors suggests that a limited number of key regulatory genes govern lineage commitment. Several transcription factors have been implicated as key regulators, positive or negative, of myeloid lineage commitment and terminal differentiation. Evidence for an autocrine mechanism involving interleukin-6 in coupling late stages of myeloid cell proliferation to cell maturation is presented. Elucidation of molecular events that take place in cell cycle control associated with growth arrest and differentiation would further enhance the understanding of the genetic programs that govern myeloid cell development.
大量证据表明，造血细胞因子及其在髓系祖细胞膜表面同源受体的可用性在谱系定向和分化中起关键作用。对于这些受体如何与下游信号转导途径偶联，从而将细胞外信号转化为遗传程序的变化，人们了解甚少。髓系祖细胞的谱系转换表明，有限数量的关键调控基因控制着谱系定向。几种转录因子已被认为是髓系谱系定向和终末分化的关键调控因子，无论是正向还是负向。本文提出了一种涉及白细胞介素-6的自分泌机制，该机制将髓系细胞增殖的后期与细胞成熟偶联起来。阐明与生长停滞和分化相关的细胞周期控制中发生的分子事件，将进一步加深对控制髓系细胞发育的遗传程序的理解。
