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Nf1 mutant mice with p19ARF gene loss develop accelerated hematopoietic disease resembling acute leukemia with a variable phenotype.
MedLine Citation:
PMID:  21681782     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Juvenile Myelomonocytic Leukemia (JMML) is a relentlessly progressive myeloproliferative/myelodysplastic (MPD/MDS) hematopoietic disorder more common in patients with any one of at least three distinct genetic lesions, specifically NF1 gene loss and PTPN11 and NRAS mutations. NF1 and PTPN11 are molecular lesions associated with Neurofibromatosis Syndrome Type I (NF1 Syndrome) and Noonan's Syndrome, respectively. The occurrence of JMML is rare; even among those predisposed with these syndromes to development of disease, and secondary genetic events likely contribute to the development and progression of disease. In NF1 syndrome, loss of p53 function is a common event in solid tumors, but uncommon in JMML, suggesting that the p53 pathway may be modified by other events in this hematopoietic disorder. The work presented here investigates the possible role of the p19(Arf) (p19) tumor suppressor in development of MPD associated with Nf1 gene loss in mice. We find that Nf1 mutant hematopoietic cells with loss of p19 develop accelerated hematopoietic disease similar to acute leukemia with a variable phenotype. This suggests that p19 may play a role in development of JMML and evaluation of the human p19 homolog (p14(ARF) ) in JMML may be informative. Am. J. Hematol. 86:579-585, 2011. © 2011 Wiley-Liss, Inc.
Authors:
Stephen M Wiesner; Jennifer L Geurts; Miechaleen D Diers; Rachel J Bergerson; Diane E Hasz; Kelly J Morgan; David A Largaespada
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  American journal of hematology     Volume:  86     ISSN:  1096-8652     ISO Abbreviation:  Am. J. Hematol.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7610369     Medline TA:  Am J Hematol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  579-85     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Wiley-Liss, Inc.
Affiliation:
Center for Allied Health Programs, University of Minnesota, Minneapolis, Minnesota; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
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