Monday, April 25, 2016
Pacritinib's Potential to Eradicate Therapy-Resistant Leukemia Stem Cells
Findings from an investigator-sponsored preclinical study have been released indicating that pacritinib, an inhibitor of JAK2, FLT3, IRAK1 and CSF1R, may be effective in reducing survival of myelofibrosis and acute myeloid leukemia (AML) repopulating cells. Further, this study also demonstrated the combination of pacritinib at low nanomolar concentrations with dasatinib may eliminate self-renewing leukemia stem cells in blast crisis of chronic myeloid leukemia (CML) with minimal toxicity toward normal progenitors. In myeloid leukemias, these leukemic stem cells can evade initial treatment and hide within the bone marrow microenvironment, develop resistance to current therapies, self-renew and eventually cause relapse.
These findings were presented by Larissa Balaian, PhD, from the Moores Cancer Center, University of California San Diego, in a poster presentation (Abstract 3338) titled: "Pacritinib Reduces Human Myeloid Leukemia Stem Cell Maintenance in a Defined Niche," during the American Association of Cancer Research Annual Meeting held April 16-20 in New Orleans.
"The potential ability for pacritinib to eradicate therapy resistant leukemia stem cells in relapse AML as a single-agent, as well as eliminate self-renewing stem cells in CML, when used in combination with standard of care therapy, demonstrates that targeting niche-dependent signaling with pacritinib could represent a new approach to treating patients with refractory acute myeloid leukemia and blast crisis of CML," said Balaian.