Retinoic Acid-Induced Expression of CD38 Antigen in Myeloid Cells is Mediated through Retinoic Acid Receptor-α

Johannes Drach, Teresa McQueen, Heike Engel, Michael Andreeff, Kent A. Robertson, Steven J. Collins, Fabio Malavasi, Kapil Mehta

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106 Scopus citations

Abstract

CD38 is a leukocyte differentiation antigen that has been thought to be a phenotypic marker of different subpopulations of T-and B-lymphocytes. In myeloid cells, CD38 is expressed during early stages of differentiation. Virtually no information is available on regulation and functions of CD38. Recently we reported that all-Zra/is-retinoic acid (ATRA) is a potent and highly specific inducer of CD38 expression in human promyelocytic leukemia cells. Here we report that ATRA-induced expression of CD38 antigen in myeloid cells is mediated through retinoic acid-α receptor (RARα). ATRA failed to induce CD38 expression in a mutant subclone of the HL-60 myeloid leukemia cell line (designated HL-60R) that is relatively resistant to ATRA-induced granulocytic differentiation. Retroviral vector-mediated transduction of RA receptor (RARα) into this HL-60R subclone completely restored the sensitivity of these cells to ATRA in terms of their ability to express CD38. In contrast, CD38 expression was not inducible by ATRA in HL-60R cells, transfected with a functional RARβ, RARγ, or RXRa receptor. Induction of CD38 in acute promyelocytic and acute myeloblasts leukemia cells was independent of ATRA-induced cytodifferentiation. Following culture with ATRA, increased CD38 protein levels were also observed in normal CD34+ bone marrow cells, but not on normal circulating granulocytes. From these results, we conclude that CD38 is ATRA inducible in myeloid leukemia cells and normal CD34+ bone marrow cells. This effect is independent of differentiation and is mediated by RARα in HL-60 cells, suggesting a similar role for RARα in CD38 expression in other hematopoietic cells.

Original languageEnglish (US)
Pages (from-to)1746-1752
Number of pages7
JournalCancer Research
Volume54
Issue number7
StatePublished - Apr 1994

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Drach, J., McQueen, T., Engel, H., Andreeff, M., Robertson, K. A., Collins, S. J., Malavasi, F., & Mehta, K. (1994). Retinoic Acid-Induced Expression of CD38 Antigen in Myeloid Cells is Mediated through Retinoic Acid Receptor-α. Cancer Research, 54(7), 1746-1752.