NPM-RAR, not the RAR-NPM reciprocal t(5;17)(q35;q21) acute promyelocytic leukemia fusion protein, inhibits myeloid differentiation

Leuk Lymphoma. 2014 Jun;55(6):1383-7. doi: 10.3109/10428194.2013.830303. Epub 2013 Sep 18.

Abstract

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.

Keywords: Acute promyelocytic leukemia; NPM–RAR; RAR–NPM; U937; differentiation; nucleophosmin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Chromosomes, Human, Pair 17*
  • Chromosomes, Human, Pair 5*
  • Gene Expression
  • Humans
  • Leukemia, Promyelocytic, Acute / genetics*
  • Leukemia, Promyelocytic, Acute / pathology*
  • Neoplasm Grading
  • Oncogene Proteins, Fusion / genetics*
  • Translocation, Genetic*

Substances

  • NPM-RARalpha protein, human
  • Oncogene Proteins, Fusion