Sox4 cooperates with CREB in myeloid transformation

Salemiz Sandoval, Christina Kraus, Er Chieh Cho, Michelle Cho, Juraj Bies, Elena Manara, Benedetta Accordi, Elliot M. Landaw, Linda Wolff, Martina Pigazzi, Kathleen M. Sakamoto

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The cAMP response element-binding protein (CREB) is a nuclear transcription factor that is critical for normal and neoplastic hematopoiesis. Previous studies have demonstrated that CREB is a proto-oncogene whose overexpression promotes cellular proliferation in hematopoietic cells. Transgenic mice that overexpress CREB in myeloid cells develop a myeloproliferative disease with splenomegaly and aberrant myelopoiesis. However, CREB overexpressing mice do not spontaneously develop acute myeloid leukemia. In this study, we used retroviral insertional mutagenesis to identify genes that accelerate leukemia in CREB transgenic mice. Our mutagenesis screen identified several integration sites, including oncogenes Gfi1, Myb, and Ras. The Sox4 transcription factor was identified by our screen as a gene that cooperates with CREB in myeloid leukemogenesis. We show that the transduction of CREB transgenic mouse bone marrow cells with a Sox4 retrovirus increases survival and selfrenewal of cells in vitro. Furthermore, leukemic blasts from the majority of acute myeloid leukemia patients have higher CREB, phosphorylated CREB, and Sox 4 protein expression. Sox4 transduction of mouse bone marrow cells results in increased expression of CREB target genes. We also demonstrate that CREB is a direct target of Sox4 by chromatin immunoprecipitation assays. These results indicate that Sox4 and CREBcooperate and contribute to increased proliferation of hematopoietic progenitor cells.

Original languageEnglish
Pages (from-to)155-165
Number of pages11
JournalBlood
Volume120
Issue number1
DOIs
Publication statusPublished - Jul 5 2012
Externally publishedYes

Fingerprint

Cyclic AMP Response Element-Binding Protein
Transgenic Mice
Mutagenesis
Genes
Acute Myeloid Leukemia
Bone Marrow Cells
Bone
Transcription Factors
myb Genes
Cells
Myelopoiesis
Proto-Oncogenes
Chromatin Immunoprecipitation
Insertional Mutagenesis
Splenomegaly
Hematopoiesis
Myeloid Cells
Retroviridae
Hematopoietic Stem Cells
Chromatin

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Sandoval, S., Kraus, C., Cho, E. C., Cho, M., Bies, J., Manara, E., ... Sakamoto, K. M. (2012). Sox4 cooperates with CREB in myeloid transformation. Blood, 120(1), 155-165. https://doi.org/10.1182/blood-2011-05-357418

Sox4 cooperates with CREB in myeloid transformation. / Sandoval, Salemiz; Kraus, Christina; Cho, Er Chieh; Cho, Michelle; Bies, Juraj; Manara, Elena; Accordi, Benedetta; Landaw, Elliot M.; Wolff, Linda; Pigazzi, Martina; Sakamoto, Kathleen M.

In: Blood, Vol. 120, No. 1, 05.07.2012, p. 155-165.

Research output: Contribution to journalArticle

Sandoval, S, Kraus, C, Cho, EC, Cho, M, Bies, J, Manara, E, Accordi, B, Landaw, EM, Wolff, L, Pigazzi, M & Sakamoto, KM 2012, 'Sox4 cooperates with CREB in myeloid transformation', Blood, vol. 120, no. 1, pp. 155-165. https://doi.org/10.1182/blood-2011-05-357418
Sandoval S, Kraus C, Cho EC, Cho M, Bies J, Manara E et al. Sox4 cooperates with CREB in myeloid transformation. Blood. 2012 Jul 5;120(1):155-165. https://doi.org/10.1182/blood-2011-05-357418
Sandoval, Salemiz ; Kraus, Christina ; Cho, Er Chieh ; Cho, Michelle ; Bies, Juraj ; Manara, Elena ; Accordi, Benedetta ; Landaw, Elliot M. ; Wolff, Linda ; Pigazzi, Martina ; Sakamoto, Kathleen M. / Sox4 cooperates with CREB in myeloid transformation. In: Blood. 2012 ; Vol. 120, No. 1. pp. 155-165.
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