Eltrombopag can decrease leukemia cell proloferation

[Birgitta-A]

Hi all,
Now we can read the abstracts from the 2007 ASH conference in Atlanta. You google ASH 2007, register and read the abstracts - there are many about MDS.

Here is a short cut from a very interesting abstract about Eltrombopag, that stimulate platelets like AMG 531. Eltrombopag seems to decrease proliferation of leukemia cells:

"Eltrombopag Decreases Proliferation of Human Leukemia and Lymphoma Cell Lines In Vitro

Connie L. Erickson-Miller, Parrish L. Payne, Sherri Moore, Sherryann Wert, Richard D. May GlaxoSmithKline, Collegeville, PA, USA; Southern Research Institute, Birmingham, AL, USA

Eltrombopag is a novel, oral platelet growth factor that interacts with the thrombopoietin receptor on bone marrow progenitors to stimulate megakaryocyte and platelet production...

...However, the addition of Eltrombopag to recombinant human thrombopoietin negated the increased proliferation seen with recombinant human thrombopoietin alone. Even more remarkable, treatment with Eltrombopag alone inhibited the proliferation of all five leukemia and lymphoma cell lines with an 50% inhibition range of 0.56 to 5.9 ug/mL and 100% inhibition of thymidine incorporation at 10 ug/mL.

Previous studies have shown that Eltrombopag induces proliferation and differentiation of bone marrow progenitor cells in vitro and increases platelet counts in vivo. While Eltrombopag and recombinant human thrombopoietin interact with the thrombopoietin receptor to stimulate the production of platelets, there are differences in the site of receptor interaction and their signaling pathways.

The findings of the current study suggest that Eltrombopag may inhibit the proliferation of leukemia and lymphoma cell lines unlike the effect that has been demonstrated with recombinant human thrombopoietin.

Interestingly, Eltrombopag may also serve to mitigate recombinant human thrombopoietin-mediated proliferation of malignant hematologic cell lines. These findings merit further evaluation of the effects of Eltrombopag on leukemia , lymphoma, and solid tumor cell proliferation."
Kind regards
Birgitta

[Neil Cuadra]

Eltrombopag, which has trade names Promacta and Revolade, is a product of U.K. pharmaceutical company GlaxoSmithKline. They developed eltrombopag in partnership with Ligand Pharmaceuticals of San Diego, CA.

The one-a-day tablet is being tested for treatment of both chemotherapy-induced thrombocytopenia and for hepatitis C. It is undergoing Phase II and Phase III clinical trials.

Eltrombopag does not yet have regulatory approval. In October, GlaxoSmithKline said it plans to submit an NDA (New Drug Application) by the end of 2007, for the treatment of short-term immune thrombocytopenic purpura (ITP) with Promacta.