SALL4, a novel oncogene, is constitutively expressed in human acute myeloid leukemia ( AML) and induces AML in transgenic mice.
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 reverse-transcription-polymerase chain reaction (RT-PCR), we demonstrated that SALL4 was constitutively expressed in human primary acute myeloid leukemia ( 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 beta-catenin and synergistically enhanced the Wnt/ beta-catenin signaling pathway. Our data suggest that the constitutive expression of SALL4 causes MDS/ AML, most likely through the Wnt/ beta-catenin pathway. Our murine model provides a useful platform to study human MDS/ AML transformation, as well as the Wnt/ beta-catenin pathway's role in the pathogenesis of leukemia stem cells.[1]References
- SALL4, a novel oncogene, is constitutively expressed in human acute myeloid leukemia (AML) and induces AML in transgenic mice. Ma, Y., Cui, W., Yang, J., Qu, J., Di, C., Amin, H.M., Lai, R., Ritz, J., Krause, D.S., Chai, L. Blood (2006) [Pubmed]
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