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CREB regulates Meis1 expression in normal and malignant hematopoietic cells

Leukemia volume 22, pages 665–667 (2008)Cite this article

CREB is a 43 kDa basic leucine zipper nuclear protein that is ubiquitously expressed and conserved from Drosophila to humans. Transcriptional activation by CREB is mediated through its interaction with a consensus octanucleotide sequence (TGANNTCA) termed the cyclic AMP response element or CRE, located in the promoter region of target genes. CREB constitutively binds to the CRE sequence as a heterodimer or a homodimer. The transcriptional activity of CREB is in part regulated by phosphorylation of the protein at a specific residue, serine 133.1, 2 Stimulation of myeloid cells by granulocyte–macrophage colony stimulating factor leads to the phosphorylation of CREB at serine 133 through an MEKK and pp90RSK (ribosomal S6 kinase)-dependent pathway.3

CREB has previously been shown to be upregulated in the majority of acute leukemias, both at diagnosis and relapse. In contrast, CREB expression was found to be lower in bone marrow cells of patients with acute leukemia in remission and in the marrow of healthy donors.4 We previously studied the biological consequences of CREB-overexpression in myeloid leukemia cells and identified CREB as a proto-oncogene involved in transformation by promoting abnormal proliferation and survival of myeloid cells. Transgenic mice in which CREB is overexpressed in the myeloid lineage developed myeloproliferative disease/myelodysplastic syndrome after 1 year.5

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Acknowledgements

We thank Jerry Cheng, Carla Gonzalez, Dejah Judelson and Bita Bahrami for technical assistance. We are grateful to Chris Denny, Linda Baum and Ken Dorshkind for helpful suggestions. This work was supported by National Institutes of Health Grants HL75826 (KMS and SE), HL83077 (KMS), American Cancer Society Grant RSG-99-081-01-LIB (KMS) and Department of Defense Grant CM050077 (KMS).

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories and Mattel Children's Hospital at UCLA, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, Los Angeles, CA, USA

    S D Esparza, J Chang & K M Sakamoto

  2. Discovery Biology, Jubilant Biosys Ltd #96, Bangalore, India

    D B Shankar

  3. Rosetta Inpharmatics—Merck Research Laboratories, Seattle, WA, USA

    B Zhang

  4. Department of Human Genetics, David Geffen School of Medicine, Los Angeles, CA, USA

    S F Nelson

  5. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, Los Angeles, CA, USA

    K M Sakamoto

  6. Molecular Biology Institute, UCLA, Los Angeles, CA, USA

    K M Sakamoto

  7. Division of Biology, California Institute of Technology, Pasadena, CA, USA

    K M Sakamoto

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  1. S D Esparza
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  2. J Chang
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  6. K M Sakamoto
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Correspondence to K M Sakamoto.

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Esparza, S., Chang, J., Shankar, D. et al. CREB regulates Meis1 expression in normal and malignant hematopoietic cells. Leukemia 22, 665–667 (2008). https://doi.org/10.1038/sj.leu.2404933

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