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Blood, 1 July 2006, Vol. 108, No. 1, pp. 297-304. Prepublished online as a Blood First Edition Paper on February 28, 2006; DOI 10.1182/blood-2005-12-5014. This Article Full Text (PDF) Supplemental Tables All Versions of this Article: 2005-12-5014v1 108/1/297    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hess, J. L Articles by Slany, R. K Search for Related Content PubMed PubMed Citation Articles by Hess, J. L Articles by Slany, R. K Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 20, 2005 Accepted February 16, 2006 c-Myb is an essential downstream target for homeobox mediated transformation of hematopoietic cells Jay L Hess, Claudia B Bittner, Deniz T Zeisig, Christian Bach, Uta Fuchs, Arndt Borkhardt, Jon Frampton, and Robert K Slany* Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA Department of Genetics, University of Erlangen, Erlangen, Germany Pediatric Hematology & Oncology, Dr. von Hauner Children's Hospital, Munich, Germany Division of Immunity and Infection, Birmingham University Medical School, Birmingham, United Kingdom * Corresponding author; email: rslany{at}biologie.uni-erlangen.de. Abdominal-type HoxA genes in combination with Meis1 are well documented oncogenes in various leukemias but it is unclear how they exert their transforming function. Here we used a system of conditional transformation by an inducible MLL-ENL oncoprotein to overexpress Hoxa9 and Meis1 in primary hematopoietic cells. Arrays identified c-Myb and a c-Myb target (Gstm1) amongst the genes with the strongest response to Hoxa9/Meis1. c-Myb overexpression was verified by Northern blot and quantitative RT-PCR. Also MLL-ENL activated c-Myb through upregulation of Hoxa9 and Meis1. Consequently short term suppression of c-Myb by siRNA efficiently inhibited transformation by MLL-ENL but did not impair transformation by E2A-HLF. The anti c-Myb siRNA effect was abrogated by coexpression of a c-Myb derivative with a mutated siRNA target site. The introduction of a dominant negative c-Myb mutant had a similar but weaker effect on MLL-ENL mediated transformation. Hematopoietic precursors from mice homozygous for a hypomorphic c-Myb allele were more severely affected and could neither be transformed by MLL-ENL nor by E2A-HLF. Ectopic expression of c-Myb induced a differentiation block but c-Myb alone was not transforming in a replating assay similar to Hoxa9/Meis1. These results suggest that c-Myb is essential but not sufficient for Hoxa9/Meis1 mediated transformation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Schwieger, A. Schuler, M. Forster, A. Engelmann, M. A. Arnold, R. Delwel, P. J. Valk, J. Lohler, R. K. Slany, E. N. Olson, et al. Homing and invasiveness of MLL/ENL leukemic cells is regulated by MEF2C Blood, September 17, 2009; 114(12): 2476 - 2488. [Abstract] [Full Text] [PDF] R. K. Slany The molecular biology of mixed lineage leukemia Haematologica, July 1, 2009; 94(7): 984 - 993. [Abstract] [Full Text] [PDF] S. R. Horman, C. S. Velu, A. Chaubey, T. Bourdeau, J. Zhu, W. E. Paul, B. Gebelein, and H. L. Grimes Gfi1 integrates progenitor versus granulocytic transcriptional programming Blood, May 28, 2009; 113(22): 5466 - 5475. [Abstract] [Full Text] [PDF] M. R. Lidonnici, F. Corradini, T. Waldron, T. P. Bender, and B. Calabretta Requirement of c-Myb for p210BCR/ABL-dependent transformation of hematopoietic progenitors and leukemogenesis Blood, May 1, 2008; 111(9): 4771 - 4779. [Abstract] [Full Text] [PDF] B. Argiropoulos, E. Yung, and R. K. Humphries Unraveling the crucial roles of Meis1 in leukemogenesis and normal hematopoiesis Genes & Dev., November 15, 2007; 21(22): 2845 - 2849. [Full Text] [PDF] E. Clappier, W. Cuccuini, A. Kalota, A. Crinquette, J.-M. Cayuela, W. A. Dik, A. W. Langerak, B. Montpellier, B. Nadel, P. Walrafen, et al. The C-MYB locus is involved in chromosomal translocation and genomic duplications in human T-cell acute leukemia (T-ALL), the translocation defining a new T-ALL subtype in very young children Blood, August 15, 2007; 110(4): 1251 - 1261. [Abstract] [Full Text] [PDF] E. Morgado, S. Albouhair, and C. Lavau Flt3 is dispensable to the Hoxa9/Meis1 leukemogenic cooperation Blood, May 1, 2007; 109(9): 4020 - 4022. [Abstract] [Full Text] [PDF] G. Jin, Y. Yamazaki, M. Takuwa, T. Takahara, K. Kaneko, T. Kuwata, S. Miyata, and T. Nakamura Trib1 and Evi1 cooperate with Hoxa and Meis1 in myeloid leukemogenesis Blood, May 1, 2007; 109(9): 3998 - 4005. [Abstract] [Full Text] [PDF]

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