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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2726-2735.
Prepublished online as a Blood First Edition Paper on June 8, 2006; DOI 10.1182/blood-2006-02-001594.
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Submitted February 3, 2006
Accepted May 24, 2006
SALL4, a novel oncogene, is constitutively expressed in human acute myeloid leukemia (AML) and induces AML in transgenic mice
Yupo Ma, Wei Cui, Jianchang Yang, Jun Qu, Chunhui Di, Hesham M Amin, Raymond Lai, Jerome Ritz, Diane S Krause, and Li Chai*
Division of Laboratory Medicine, Nevada Cancer Institute, USA
Brigham and Women's Hospital/Children's Hospital, USA
University of Texas, M.D. Anderson Cancer Center, USA
University of Alberta, Canada
Dana-Farber Institute/Harvard Medical School, USA
The Department of Laboratory Medicine, Yale University, USA
Brigham and Women's Hospital/Harvard Medical School, USA
* Corresponding author; email: lchai{at}partners.org.
SALL4, a human homolog to Drosophila spalt, is a novel zinc finger transcriptional factor essential for development. We cloned SALL4 and its isoforms (SALL4A and SALL4B). Through immunohistochemistry and real-time RT-PCR, we demonstrated that SALL4 was constitutively expressed in human primary AML (N=81), and directly tested the leukemogenic potential of constitutive expression of SALL4 in a murine model. SALL4B transgenic mice developed myelodysplastic syndrome (MDS)-like features and subsequently AML that was transplantable. Increased apoptosis associated with dysmyelopoiesis was evident in transgenic mouse marrow and colony-formation (CFU) assays. Both isoforms could bind to  -catenin and synergistically enhanced the Wnt/-catenin signaling pathway. Our data suggest that the constitutive expression of SALL4 causes MDS/AML, most likely through the Wnt/-catenin pathway. Our murine model provides a useful platform to study human MDS/AML transformation, as well as the Wnt/-catenin pathway's role in the pathogenesis of leukemia stem cells.
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