E2A is a transcriptional regulator of CD38 expression in chronic lymphocytic leukemia

I. Saborit-Villarroya, T. Vaisitti, D. Rossi, G. D'Arena, G. Gaidano, F. Malavasi, S. Deaglio

Research output: Contribution to journalArticle

Abstract

CD38, a nucleotide-metabolizing ectoenzyme and a receptor, is a negative prognostic marker for chronic lymphocytic leukemia (CLL) patients. CD38 has a genetic polymorphism, with a C G variation in a putative E-box located in a regulatory region. E2A, the predominant E-box factor in B lymphocytes, was found to be highly expressed by CD38 CLL patients. The highest CD38 levels scored by E2A /G carrier patients suggested that E2A is (i) directly associated with CD38 expression, and that (ii) the binding of the transcription factor is influenced by the CD38 genotype. Chromatin immunoprecipitation indicated that E2A directly interacts with the CD38 regulatory region. Furthermore, E2A binding was stronger in the presence of the G allele. Experiments of E2A silencing led to a significant reduction of surface levels of CD38, confirming the working hypothesis. A direct functional interplay between E2A and CD38 was shown by exposing CLL cells to interleukin-2 and TLR-9 ligands, both inducers of CD38 expression. Under these conditions, CD38 upregulation was primarily conditioned by the presence of E2A and then by the G allele. The results of this study link E2A and CD38 expression within a common pathway, in which E-protein activity is required for the efficient induction of CD38 transcription.

Original languageEnglish
Pages (from-to)479-488
Number of pages10
JournalLeukemia
Volume25
Issue number3
DOIs
Publication statusPublished - Mar 2011

Fingerprint

B-Cell Chronic Lymphocytic Leukemia
Nucleic Acid Regulatory Sequences
Alleles
Chromatin Immunoprecipitation
Genetic Polymorphisms
Interleukin-2
B-Lymphocytes
Transcription Factors
Up-Regulation
Nucleotides
Genotype
Ligands
Proteins

Keywords

  • CD38
  • chronic lymphocytic leukemia
  • E2A
  • SNP
  • transcriptional regulation

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Saborit-Villarroya, I., Vaisitti, T., Rossi, D., D'Arena, G., Gaidano, G., Malavasi, F., & Deaglio, S. (2011). E2A is a transcriptional regulator of CD38 expression in chronic lymphocytic leukemia. Leukemia, 25(3), 479-488. https://doi.org/10.1038/leu.2010.291

E2A is a transcriptional regulator of CD38 expression in chronic lymphocytic leukemia. / Saborit-Villarroya, I.; Vaisitti, T.; Rossi, D.; D'Arena, G.; Gaidano, G.; Malavasi, F.; Deaglio, S.

In: Leukemia, Vol. 25, No. 3, 03.2011, p. 479-488.

Research output: Contribution to journalArticle

Saborit-Villarroya, I, Vaisitti, T, Rossi, D, D'Arena, G, Gaidano, G, Malavasi, F & Deaglio, S 2011, 'E2A is a transcriptional regulator of CD38 expression in chronic lymphocytic leukemia', Leukemia, vol. 25, no. 3, pp. 479-488. https://doi.org/10.1038/leu.2010.291
Saborit-Villarroya I, Vaisitti T, Rossi D, D'Arena G, Gaidano G, Malavasi F et al. E2A is a transcriptional regulator of CD38 expression in chronic lymphocytic leukemia. Leukemia. 2011 Mar;25(3):479-488. https://doi.org/10.1038/leu.2010.291
Saborit-Villarroya, I. ; Vaisitti, T. ; Rossi, D. ; D'Arena, G. ; Gaidano, G. ; Malavasi, F. ; Deaglio, S. / E2A is a transcriptional regulator of CD38 expression in chronic lymphocytic leukemia. In: Leukemia. 2011 ; Vol. 25, No. 3. pp. 479-488.
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