Fichelson S, Vigon I, Dusanter I, Charon M, Velu T, Baillou C, Gisselbrecht S, Lemoine F M
INSERM U363, ICGM, René Descartes University, Paris, France.
J Immunol. 1995 Feb 15;154(4):1577-86.
v-mpl is a constitutively activated, truncated form of a cytokine receptor that has been transduced in a murine retrovirus, the myeloproliferative leukemia virus (MPLV). Expression of this oncogene results in the factor-independent proliferation of myeloid, erythroid, megakaryocytic, and mast precursor cells, which retain the ability to differentiate. However, no lymphoid disease was ever reported. To determine whether MPLV could infect and transform very early B cells and their precursors (BCPs), lymphoid long-term bone marrow cultures were infected with a helper-free MPLV. Within 3 wk after infection, highly proliferating BCPs could be isolated. These cells were able to clone spontaneously in semi-solid cultures, grown in the absence of feeder cell layer or exogenous growth factor and rapidly produced tumors after s.c. injection into synegic irradiated mice. In addition, MPLV transformation of pre-B cells led to the induction of an autocrine activity. Immunophenotypic and molecular analysis indicated that MPLV transformed early pro-B, pro-B, and pre-B cells, according to the expression of HSA, CD43, B220, Thy1, s-IgM and BP1 Ags, and to the rearrangements of Ig genes. Interestingly, MPLV-transformed BCPs expressed Mac1 Ag without acquiring further characteristics of macrophagic differentiation. Although the v-mpl cytoplasmic domain is devoid of tyrosine kinase consensus sequence, MPLV-transformed pre-B cells contained a major approximately 105-kDa tyrosine-phosphorylated protein that was not detected in uninfected cells or in cells transformed by the Abelson viral oncogene (v-abl). These results demonstrate that, like v-abl, the truncated cytokine receptor v-mpl is able to transform BCPs in vitro and suggest that the oncogenic transformation of BCPs by either v-mpl or v-abl use different pathways.
v-mpl是一种细胞因子受体的组成型激活截短形式，已在鼠逆转录病毒——骨髓增殖性白血病病毒（MPLV）中发生转导。该癌基因的表达导致髓系、红系、巨核系和肥大前体细胞的因子非依赖性增殖，这些细胞保留了分化能力。然而，从未有过淋巴样疾病的报道。为了确定MPLV是否能够感染并转化极早期B细胞及其前体（BCP），将无辅助病毒的MPLV感染淋巴样长期骨髓培养物。感染后3周内，可分离出高度增殖的BCP。这些细胞能够在半固体培养物中自发克隆，在无饲养细胞层或外源性生长因子的情况下生长，并在皮下注射到同基因照射小鼠后迅速产生肿瘤。此外，MPLV对前B细胞的转化导致自分泌活性的诱导。免疫表型和分子分析表明，根据HSA、CD43、B220、Thy1、s-IgM和BP1抗原的表达以及Ig基因的重排，MPLV转化了早期前B细胞、前B细胞和前B细胞。有趣的是，MPLV转化的BCP表达Mac1抗原，但未获得巨噬细胞分化的进一步特征。尽管v-mpl胞质结构域缺乏酪氨酸激酶共有序列，但MPLV转化的前B细胞含有一种主要的约105 kDa酪氨酸磷酸化蛋白，在未感染细胞或由Abelson病毒癌基因（v-abl）转化的细胞中未检测到。这些结果表明，与v-abl一样，截短的细胞因子受体v-mpl能够在体外转化BCP，并提示v-mpl或v-abl对BCP的致癌转化使用不同的途径。
