NPM-RAR, not the RAR-NPM reciprocal t(5;17)(q35;q21) acute promyelocytic leukemia fusion protein, inhibits myeloid differentiation.
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.
Department of Medicine and University of Pittsburgh Cancer Institute, University of Pittsburgh , Pittsburgh, PA , USA.
Sheri L
SL
Pollock
Elizabeth A
EA
Rush
Robert L
RL
Redner
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002886:Chromosomes, Human, Pair 17; D002895:Chromosomes, Human, Pair 5; D015870:Gene Expression; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000473:pathology*; D060787:Neoplasm Grading; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D014178:Translocation, Genetic
C120276:NPM-RARalpha protein, human; D015514:Oncogene Proteins, Fusion
Acute promyelocytic leukemia; NPM–RAR; RAR–NPM; U937; differentiation; nucleophosmin