Acceleration of chronic myeloproliferation by enforced expression of Meis1 or Meis3 in Icsbp-deficient bone marrow cells

Homing and invasiveness of MLL/ENL leukemic cells is regulated by MEF2C

“…Notably, many of the downstream targets of MLL fusion proteins have complementary but also overlapping transforming properties. 5,6,39 Alternatively, loss of Mef2c may be compensated by up-regulation of other Mef2 proteins in these cells. We did not observe up-regulation of Mef2d expression in these tumors (M.S., S. Roscher, C.S., unpublished results, June 2007), but we cannot rule out that expression of Mef2a or Mef2b is affected.…”

Regulation of myelopoiesis by the transcription factor IRF8

“…IRF8 deficiency synergizes with the oncogenes, such as AML1-ETO, NUP98-TOP1, and Meis1/3, to induce myeloblastic transformation [65][66][67]. Furthermore, forced IRF8 coexpression overcomes the in vitro mitogenic and anti-apoptotic activities of BCR-ABL-which is the causal oncoprotein for CML [62,64]-and inhibits BCR-ABL-induced mouse myeloproliferative disorder in vivo [59].…”

Cross talk between Wnt/β-catenin and Irf8 in leukemia progression and drug resistance

“…Down-regulation of Irf8 is required for murine BCR-ABL–inducible CML disease, whereas coexpression of Irf8 repressed the mitogenic activity of BCR-ABL in vivo (Hao and Ren, 2000) and in vitro (Tamura et al, 2003; Burchert et al, 2004). Loss of Irf8 synergized with different oncogenes and induced myeloblastic transformation (Schwieger et al, 2002; Gurevich et al, 2006; Hara et al, 2008); however, progression of Irf8 −/− CML-like disease in mice occurred rarely and only after long latency (Holtschke et al, 1996). These results suggested that Irf8 deficiency is a prerequisite but not sufficient for malignant transformation and requires an additional genetic lesion for blast crisis progression.…”