NEOPLASIA Brief report Runx1 deficiency predisposes mice to T-lymphoblastic lymphoma

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 nor-mal function of the Runt-related transcrip-tion factor 1 (RUNX)/core binding factor (CBF) complexes. In addition, loss-of-function mutations in Runt-related transcrip-tion 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 devel-opment of leukemia, we treated chimeric mice generated from Runx1lacZ/lacZ embry-onic stem (ES) cells that have homozygous disruption of the Runx1 gene with N-ethyl-N-nitrosourea (ENU). We observed an in-creased incidence of T-lymphoblastic lym-phoma in Runx1lacZ/lacZ compared with wild-typechimerasandconfirmedthat the tumors were of ES-cell origin. Our results therefore suggest that deficiency of Runx1 can in-deed predispose mice to hematopoietic ma-lignancies. (Blood. 2005;106:3621-3624) © 2005 by The American Society of Hematolog