NPM-RAR而非RAR-NPM相互易位t(5;17)(q35;q21)急性早幼粒细胞白血病融合蛋白抑制髓系分化。
NPM-RAR, not the RAR-NPM reciprocal t(5;17)(q35;q21) acute promyelocytic leukemia fusion protein, inhibits myeloid differentiation.
作者信息
Pollock Sheri L, Rush Elizabeth A, Redner Robert L
机构信息
Department of Medicine and University of Pittsburgh Cancer Institute, University of Pittsburgh , Pittsburgh, PA , USA.
出版信息
Leuk Lymphoma. 2014 Jun;55(6):1383-7. doi: 10.3109/10428194.2013.830303. Epub 2013 Sep 18.
The t(5;17) variant of acute promyelocytic leukemia (APL) fuses the nucleophosmin (NPM) gene at 5q35 with the retinoic acid receptor alpha (RARA) at 17q12-22. We have previously shown that leukemic cells express both NPM-RAR and RAR- NPM reciprocal translocation products. In this study we investigated the potential role of both proteins in modulating myeloid differentiation. Expression of NPM-RAR inhibited vitamin D3/transforming growth factor β (TGFβ)-mediated differentiation of U937 cells by more than 50%. In contrast, RAR-NPM expression did not alter vitamin D3/TGFβ-induced differentiation of U937 clones. These results indicate that NPM-RAR, not RAR-NPM, is the prime mediator of myeloid differentiation arrest in t(5;17) APL.
急性早幼粒细胞白血病（APL）的t(5;17) 变异型使位于5q35的核磷蛋白（NPM）基因与位于17q12 - 22的维甲酸受体α（RARA）融合。我们之前已经表明，白血病细胞表达NPM - RAR和RAR - NPM这两种相互易位产物。在本研究中，我们调查了这两种蛋白在调节髓系分化中的潜在作用。NPM - RAR的表达抑制维生素D3/转化生长因子β（TGFβ）介导的U937细胞分化超过50%。相比之下，RAR - NPM的表达并未改变维生素D3/TGFβ诱导的U937克隆分化。这些结果表明，在t(5;17) APL中，NPM - RAR而非RAR - NPM是髓系分化阻滞的主要介导因子。
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