Runx1 promotes B-cell survival and lymphoma development.
Runx1 is essential for the homeostatic control of normal hematopoiesis and is required for lymphoid development. Translocations or point mutations that result in RUNX1 loss or disrupted function predispose to leukemia but data derived from model systems suggests that Runx genes can also be pro-oncogenic. Here we investigate the effects of enforced Runx1 expression in lymphoid lineages both in vivo and in vitro and show that transgene expression enhanced cell survival in the thymus and bone marrow but strongly inhibited the expansion of hematopoietic and B cell progenitors in vitro. Despite this, modestly enhanced levels of Runx1 accelerated Myc-induced lymphomagenesis in both the B cell and T cell lineages. Together these data provide formal proof that wild type Runx1 can promote oncogenesis in lymphoid tissues and that, in addition to loss of function, gain of function may have an aetiological role in leukemia.
Blyth
Karen
K
Faculty of Veterinary Medicine, Molecular Oncology Laboratory, Institute of Comparative Medicine, University of Glasgow, Glasgow, UK.
Slater
Nicholas
N
Hanlon
Linda
L
Bell
Margaret
M
Mackay
Nancy
N
Stewart
Monica
M
Neil
James C
JC
Cameron
Ewan R
ER
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000473:pathology*; D049109:Cell Proliferation; D002470:Cell Survival; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D008221:Lymphoid Tissue / Q000166:cytology / Q000473:pathology; D008223:Lymphoma / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000166:cytology / Q000473:pathology*
D050676:Core Binding Factor Alpha 2 Subunit; C493726:Runx1 protein, mouse