ISSN Print: 0893-9675
You have access to:Volume 20, 2015 Volume 19, 2014 Volume 18, 2013 Volume 17, 2012 Volume 16, 2011 Volume 15, 2009 Volume 14, 2008 Volume 13, 2007 Volume 12, 2006 Volume 11, 2000 Volume 9, 1998 Volume 8, 1997 Volume 7, 1996 Volume 6, 1995 Volume 5, 1994
Critical Reviews™ in Oncogenesis
The Role of Hox Proteins in Leukemogenesis: Insights Into Key Regulatory Events in Hematopoiesis
The Feinberg School at Northwestern University and Jesse Brown VA Medical Center, 303 E. Superior St., Lurie 5-105, Chicago, IL
Acute myeloid leukemia (AML) is a heterogeneous disease with highly variable prognoses. Identification of recurring chromosomal translocations provides some prognostic information for individual AML subjects. Population based gene-expression profiling studies also identified abnormalities relevant to prognosis. Such studies associate increased expression of a set of homeodomain transcription factors with poor prognosis in AML. This set includes HoxB3, B4, A7-11 and Meis1, which are dysregulated as a group in the bone marrow in poor prognosis AML. Aberrant expression of these homeodomain transcription factors is found in AML with chromosomal translocations involving the MLL, MYST3 and CREBBP genes, and in a poor prognosis subset with normal cytogenetics. Studies in murine models suggest that Hox protein overexpression is functionally significant for myeloid malignancies. Overexpression of individual Hox proteins expanded various bone marrow populations in vitro, leading to myeloproliferation and in some cases differentiation block and AML in vivo. Therefore, dysregulated expression of key Hox target genes may contribute to adverse prognosis in AML. Identification of these genes will provide insights into the pathobiology of prognosis in AML. Studies are beginning to identify Hox target genes which may be rational targets for therapeutic approaches to this poor prognosis leukemia subset.
|Home||Begell Digital Library||eBooks||Journals||References & Proceedings||Research Collections|