Faculty Collaboration Database

Nf1 mutant mice with p19ARF gene loss develop accelerated hematopoietic disease resembling acute leukemia with a variable phenotype. Am J Hematol 2011 Jul;86(7):579-85

Date

06/18/2011

Pubmed ID

21681782

Pubmed Central ID

PMC3506005

DOI

10.1002/ajh.22035

Scopus ID

2-s2.0-79959347114 (requires institutional sign-in at Scopus site)   5 Citations

Abstract

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.

Author List

Wiesner SM, Geurts JL, Diers MD, Bergerson RJ, Hasz DE, Morgan KJ, Largaespada DA

Author

Jennifer L. Geurts MS, CGC Director, Assistant Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Disease
Animals
Cyclin-Dependent Kinase Inhibitor p16
Humans
Leukemia, Myelomonocytic, Juvenile
Mice
Mice, Mutant Strains
Neurofibromatosis 1
Neurofibromin 1
Tumor Suppressor Protein p53