Characterization of the PML-RARα chimeric product of the acute promyelocytic leukemia-specific t(15;17) translocation

Clara Nervi, E. Christine Poindexter, Francesco Grignani, Pier Paolo Pandolfi, Francesco Lo Coco, Giuseppe Avvisati, Pier Giuseppe Pelicci, Anton M. Jetten

Research output: Contribution to journalArticlepeer-review

Abstract

The acute promyelocytic leukemia 15;17 chromosomal translocation fuses the PML gene to the RARα locus. The resulting chimeric gene encodes for a putative PML-RARα fusion protein. PML is a putative transcriptional factor and RARα is one of the nuclear retinoic acid receptors through which retinoic acid regulates gene expression. In this study, we investigated the retinoid binding and biochemical properties of the PML-RARα protein by size exclusion high-performance liquid chromatography and immunoblot analysis and compared them with those of normal RARα. The introduction of the expression vector PSG5/PML-RARα into COS-1 cells led to high levels of expression of the PML-RARα fusion protein. This protein was primarily localized in the nucleus and bound retinoids with the same affinity and specificity as the wild type RARα receptor. The PML-RARα fusion protein, but not the RARα, was found in high molecular weight complexes with either itself or other nuclear factors. In the acute promyelocytic leukemia-derived cell line NB4, which contains the t(15;17) chromosomal marker, the PML-RARα product was also found as a high molecular complex. The interaction of the PML-RARα with itself or with other nuclear proteins may be important in understanding the role of the PML-RARα fusion protein in promyelocytic leukemogenesis.

Original languageEnglish
Pages (from-to)3687-3692
Number of pages6
JournalCancer Research
Volume52
Issue number13
Publication statusPublished - Jul 1 1992

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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