HOX-induced acute myeloid leukemia treated by specific Flt3 inhibitors

09-29-2006

According to a study from Canada, "In leukemogenesis, several genetic changes conferring a proliferative and/or survival advantage to hematopoietic progenitor cells in addition to a block in differentiation are required. Here, we demonstrate that overexpression of the wildtype (wt) Flt3 receptor tyrosine kinase collaborates with NUP98-HOX fusions (NUP98-HOXA10 and NUP98-HOXD13) to induce aggressive AML."

"We used a mouse transplantation model to show their synergism in cotransduced bone marrow cells as well as in a cellular model of leukemic progression," explained L. Palmqvist and colleagues, British Columbia Cancer Agency. "Furthermore, our data support the finding that Meis1 overexpression leads to marked elevation in Flt3 transcription and extend it to the context of NUP98-HOX-induced leukemia.

"Together, these results support a multistep model where the synergism between NUP98-HOX and wt-Flt3 is the result of the ability of Flt3 to increase proliferation of myeloid progenitors blocked in differentiation by NUP98-HOX fusions and reveal a direct role for wt-Flt3 in the pathobiology of AML."

The researchers concluded, "Given the similarities in the leukemogenic role of native HOX and NUP98-fused HOX genes, our results underscore the clinical significance of the recurrent co-overexpression of wt-Flt3 and HOX in human leukemia and suggest that specific Flt3 inhibitors could be useful in treatment of HOX-induced AML or acute lymphoblastic leukemia (ALL)."

Palmqvist and colleagues published their study in Blood (The Flt3 receptor tyrosine kinase collaborates with NUP98-HOX fusions in acute myeloid leukemia. Blood, 2006;108(3):1030-1036).

For more information, contact R.K. Humphries, British Columbia Cancer Agency, Terry Fox Laboratory, 11th Floor, 675 W 10th Avenue, Vancouver, BC V5Z 1L3, Canada.

Publisher contact information for the journal Blood is: American Society Hematology, 1900 M Street. NW Suite 200, Washington, DC 20036, USA.

Keywords: Vancouver, British Columbia, Canada, Acute Myeloid Leukemia, Bone Marrow, Genetics, Hematology, Hematopoietic, Oncology, Proteins, Proteomics, Tyrosine Kinase, Flt3 Inhibitors.

This article was prepared by Hematology Week editors from staff and other reports. Copyright 2006, Hematology Week via NewsRx.com.