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首页> 外文期刊>Molecular and Cellular Biology >Deregulated c-myb disrupts interleukin-6- or leukemia inhibitory factor-induced myeloid differentiation prior to c-myc: role in leukemogenesis.
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Deregulated c-myb disrupts interleukin-6- or leukemia inhibitory factor-induced myeloid differentiation prior to c-myc: role in leukemogenesis.

机译：失调的c-myb在c-myc之前破坏白细胞介素6或白血病抑制因子诱导的髓样分化：在白血病发生中的作用。

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The c-myb proto-oncogene is abundantly expressed in tissues of hematopoietic origin, and changes in endogenous c-myb genes have been implicated in both human and murine hematopoietic tumors. c-myb encodes a DNA-binding protein capable of trans-activating the c-myc promoter. Suppression of both of these proto-oncogenes was shown to occur upon induction of terminal differentiation but not upon induction of growth inhibition in myeloid leukemia cells. Myeloblastic leukemia M1 cells that can be induced for terminal differentiation with the physiological hematopoietic inducers interleukin-6 and leukemia inhibitory factor were genetically manipulated to constitutively express a c-myb transgene. By using immediate-early to late genetic and morphological markers, it was shown that continuous expression of c-myb disrupts the genetic program of myeloid differentiation at a very early stage, which precedes the block previously shown to be exerted by deregulated c-myc, thereby indicating that the c-myb block is not mediated via deregulation of c-myc. Enforced c-myb expression also prevents the loss in leukemogenicity of M1 cells normally induced by interleukin-6 or leukemia inhibitory factor. Any changes which have taken place, including induction of myeloid differentiation primary response genes, eventually are reversed. Also, it was shown that suppression of c-myb, essential for terminal differentiation, is not intrinsic to growth inhibition. Taken together, these findings show that c-myb plays a key regulatory role in myeloid differentiation and substantiate the notion that deregulated expression of c-myb can play an important role in leukemogenicity.
机译：c-myb原癌基因在造血起源的组织中大量表达，并且内源性c-myb基因的变化与人类和鼠类造血肿瘤有关。 c-myb编码能够反式激活c-myc启动子的DNA结合蛋白。这两种原癌基因的抑制均显示在诱导髓样白血病细胞中终末分化时发生，而不是在诱导生长抑制时发生。可以通过生理造血诱导因子白细胞介素6和白血病抑制因子诱导分化为终末分化的骨髓小细胞白血病M1细胞，以组成型表达c-myb转基因。通过使用从早到晚的遗传和形态标记，表明c-myb的持续表达在很早的阶段就破坏了髓系分化的遗传程序，这早于先前显示的由c-myc失控发挥的作用，从而表明c-myb阻滞不是通过放松c-myc介导的。增强的c-myb表达还可以防止白细胞介素6或白血病抑制因子正常诱导的M1细胞白血病发生能力的丧失。发生的任何变化，包括诱导髓样分化初级反应基因，最终都将被逆转。另外，显示出对终末分化必不可少的c-myb抑制不是生长抑制所固有的。综上所述，这些发现表明c-myb在髓样分化中起着关键的调节作用，并证实了c-myb的表达失调可以在致白血病性中起重要作用的观点。

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