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Sox4 cooperates with CREB in myeloid transformation
Salemiz Sandoval1, Christina Kraus, Er-Chieh Cho
1Department of Pediatrics and Pathology & Laboratory Medicine, Gwynne Hazen, Cherry Memorial Laboratories, Mattel Children's Hospital, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Sox4 cooperates with CREB to drive myeloid leukemogenesis. This cooperation increases hematopoietic progenitor cell proliferation and is observed in acute myeloid leukemia patients.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- CREB (cAMP response element-binding protein) is a proto-oncogene crucial for hematopoiesis.
- CREB overexpression in myeloid cells causes myeloproliferative disease but not acute myeloid leukemia.
Purpose of the Study:
- Identify genes that accelerate leukemia development in CREB transgenic mice.
- Investigate the role of Sox4 in myeloid leukemogenesis with CREB.
Main Methods:
- Retroviral insertional mutagenesis screen in CREB transgenic mice.
- In vitro studies of bone marrow cell transduction with Sox4.
- Chromatin immunoprecipitation assays.
- Analysis of patient samples for protein expression.
Main Results:
- Sox4 was identified as a cooperating gene in myeloid leukemogenesis.
- Sox4 transduction enhanced survival and self-renewal of CREB transgenic bone marrow cells.
- Elevated CREB, phosphorylated CREB, and Sox4 protein levels were found in acute myeloid leukemia patient blasts.
- Sox4 directly targets CREB, increasing CREB target gene expression.
Conclusions:
- Sox4 and CREB cooperate to promote hematopoietic progenitor cell proliferation.
- The Sox4-CREB interaction is implicated in acute myeloid leukemia development.
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