Reduced proliferation of non-megakaryocytic acute myelogenous leukemia and other leukemia and lymphoma cell lines in response to eltrombopag.
Leukemia cell lines were treated with eltrombopag or thrombopoietin and their proliferative response was determined. Eltrombopag did not increase proliferation of cell lines that did not express high levels of megakaryocyte markers. Instead, treatment with eltrombopag alone inhibited proliferation of many cell lines (IC(50) range=0.56-21 microg/mL). The addition of other cytokines, such as G-CSF, Epo or Tpo, did not affect the decrease in proliferation. The decrease in proliferation appears to be through a TpoR-independent, nonapoptotic mechanism. These findings suggest that eltrombopag does not enhance, but rather inhibits, proliferation of leukemia cell lines in vitro.
Erickson-Miller
Connie L
CL
Oncology Translational Research, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA, USA. Connie L Erickson-Miller@GSK.com
Kirchner
Jennifer
J
Aivado
Manuel
M
May
Richard
R
Payne
Parrish
P
Chadderton
Antony
A
D001483:Base Sequence; D001565:Benzoates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology*; D007938:Leukemia / Q000473:pathology*; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008223:Lymphoma / Q000473:pathology*; D011720:Pyrazoles / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001565:Benzoates; D017931:DNA Primers; D006834:Hydrazines; D011720:Pyrazoles; C520809:eltrombopag