Mary Ann Arildsen
Faculty Member
Last active: 6/27/2014

The inv(16) cooperates with ARF haploinsufficiency to induce acute myeloid leukemia.

Moreno-Miralles I, Pan L, Keates-Baleeiro J, Durst-Goodwin K, Yang C, Kim HG, Thompson MA, Klug CA, Cleveland JL, Hiebert SW
J Biol Chem. 2005 280 (48): 40097-103

PMID: 16199529 · DOI:10.1074/jbc.M506855200

The inv(16) is one of the most frequent chromosomal translocations associated with acute myeloid leukemia (AML) and creates a chimeric fusion protein consisting of most of the runt-related X1 co-factor, core binding factor beta fused to the smooth muscle myosin heavy chain MYH11. Expression of the ARF tumor suppressor is regulated by runt-related X1, suggesting that the inv(16) fusion protein (IFP) may repress ARF expression. We established a murine bone marrow transplant model of the inv(16) in which wild type, Arf+/-, and Arf-/- bone marrow were engineered to express the IFP. IFP expression was sufficient to induce a myelomonocytic AML even when expressed in wild type bone marrow, yet removal of only a single allele of Arf greatly accelerated the disease, indicating that Arf is haploinsufficient for the induction of AML in the presence of the inv(16).

MeSH Terms (26)

Alleles Animals Bone Marrow Cells Bone Marrow Transplantation Cyclin-Dependent Kinase Inhibitor p16 DNA Flow Cytometry Genes, Reporter Green Fluorescent Proteins Humans Leukemia, Myeloid, Acute Liver Mice Mice, Transgenic Mutagenesis NIH 3T3 Cells Oncogene Proteins, Fusion Plasmids Promoter Regions, Genetic Protein Binding Recombinant Fusion Proteins Spleen Time Factors Transfection Translocation, Genetic Tumor Suppressor Protein p14ARF

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