title: Runx1 deficiency predisposes mice to T-lymphoblastic lymphoma.
abstract: Chromosomal rearrangements affecting RUNX1 and CBFB are common in acute leukemias. These mutations result in the expression of fusion proteins that act dominant-negatively to suppress the normal function of the Runt-related transcription factor 1 (RUNX)/core binding factor beta (CBFbeta) complexes. In addition, loss-of-function mutations in Runt-related transcription factor 1 (RUNX1) have been identified in sporadic cases of acute myeloid leukemia (AML) and in association with the familial platelet disorder with propensity to develop AML (FPD/AML). In order to examine the hypothesis that decreased gene dosage of RUNX1 may be a critical event in the development of leukemia, we treated chimeric mice generated from Runx1(lacZ/lacZ) embryonic stem (ES) cells that have homozygous disruption of the Runx1 gene with N-ethyl-N-nitrosourea (ENU). We observed an increased incidence of T-lymphoblastic lymphoma in Runx1(lacZ/lacZ) compared with wild-type chimeras and confirmed that the tumors were of ES-cell origin. Our results therefore suggest that deficiency of Runx1 can indeed predispose mice to hematopoietic malignancies.
authors.affiliation: Genetics and Molecular Biology Branch and Genetic Diseases Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Mondira
authors.initials: M
authors.lastname: Kundu
authors.forename: Sheila
authors.initials: S
authors.lastname: Compton
authors.forename: Lisa
authors.initials: L
authors.lastname: Garrett-Beal
authors.forename: Terryl
authors.initials: T
authors.lastname: Stacy
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Starost
authors.forename: Michael
authors.initials: M
authors.lastname: Eckhaus
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Speck
authors.forename: P Paul
authors.initials: PP
authors.lastname: Liu
mesh_terms: D000818:Animals; D002869:Chromosome Aberrations; D050676:Core Binding Factor Alpha 2 Subunit / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C493726:Runx1 protein, mouse