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首页> 外文期刊>Molecular and Cellular Biology >Alternative forms of the BCR-ABL oncogene have quantitatively different potencies for stimulation of immature lymphoid cells.
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Alternative forms of the BCR-ABL oncogene have quantitatively different potencies for stimulation of immature lymphoid cells.

机译：BCR-ABL致癌基因的替代形式在刺激未成熟淋巴样细胞方面具有数量不同的效力。

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The Philadelphia chromosome (t9:22;q34:q11) is found in more than 90% of patients with chronic myelogenous leukemia, in 10 to 20% of patients with acute lymphocytic leukemia, and in 1 to 2% of patients with acute myelogenous leukemia. Alternative chimeric oncogenes are formed by splicing different sets of BCR gene exons on chromosome 22 across the translocation breakpoint to a common set of ABL oncogene sequences on chromosome 9. This results in an 8.7-kilobase mRNA that encodes the P210 BCR-ABL gene product commonly found in patients with chronic myelogenous leukemia or a 7.0-kilobase mRNA that produces the P185 BCR-ABL gene product found in most Philadelphia chromosome-positive patients with acute lymphocytic leukemia. To compare the efficiency of growth stimulation by these two proteins, we derived cDNA clones for each with identical 5' and 3' untranslated regions and expressed them from retrovirus vectors. Matched stocks were compared for potency to transform immature B-lymphoid lineage precursors. The growth-stimulating effects of P185 for this cell type were found to be significantly greater than those of P210. Structural changes in BCR may regulate the effectiveness of the ABL tyrosine kinase function, as monitored by lymphocyte growth response. Changes in mitogenic potency may help to explain the more acute leukemic presentation usually associated with expression of the P185 BCR-ABL oncogene.
机译：费城染色体（t9：22; q34：q11）在90％以上的慢性粒细胞性白血病患者，10％至20％的急性淋巴细胞性白血病患者以及1％至2％的急性骨髓性白血病患者中被发现。通过跨染色体易位点将22号染色体上不同的BCR基因外显子剪接至9号染色体上的ABL癌基因通用序列，可以形成其他嵌合癌基因。这将产生一个8.7 kb的mRNA，通常编码P210 BCR-ABL基因产物。在患有慢性粒细胞性白血病或7.0 kb的mRNA的患者中发现，该mRNA产生在大多数费城染色体阳性的急性淋巴细胞性白血病患者中发现的P185 BCR-ABL基因产物。为了比较这两种蛋白质对生长的刺激效率，我们为每个具有相同5'和3'非翻译区的cDNA克隆，并从逆转录病毒载体表达它们。比较了匹配的股票转化未成熟B淋巴谱系前体的能力。发现P185对这种细胞类型的生长刺激作用显着大于P210。 BCR的结构变化可调节ABL酪氨酸激酶功能的有效性，如淋巴细胞生长反应所监测。有丝分裂能力的变化可能有助于解释通常与P185 BCR-ABL癌基因表达相关的更为急性的白血病表现。

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