Submitted January 19, 2006
Accepted December 26, 2006
Flt3 is dispensable to the Hoxa9/Meis1 leukemogenic
cooperation
Ester Morgado, Stephanie Albouhair, and Catherine Lavau*
CNRS, Hopital Saint-Louis, Paris, France
* Corresponding author; email: catherine.lavau{at}paris7.jussieu.fr.
HOX genes, MEIS1 and FLT3 are frequently upregulated in human myeloid leukemias. Meis1 cooperates with Hox genes to induce leukemias in mice, hypothetically the consequence of Meis1-induced Flt3 overexpression. To test this, we compared the properties of Flt3-/- and Flt3+/+ progenitors transduced with Hoxa9 or Hoxa9/Meis1. In a myeloid clonogenic assay, Meis1 greatly enhanced the proliferation of Hoxa9 expressing cells, massively upregulating Flt3 protein. However, the transforming potential of Hoxa9/Meis1 was unaltered in Flt3-/- cells. All mice transplanted with Hoxa9/Meis1-transduced progenitors succumbed to rapid acute myeloid leukemias regardless of Flt3 genotype. Flt3 expression levels in leukemic blasts did not correlate with parameters reflecting their proliferative rate or their impaired differentiation. Furthermore, analysis of c-Myb expression levels in Hoxa9/Meis1-transformed cells showed that the upregulation of this critical downstream effector was independent of Flt3. Altogether, our findings demonstrate that Flt3 is dispensable to the oncogenic cooperation of Meis1 with Hoxa9.
