Regulation of Myeloid Leukemia Cells by Platelet Factor 4

Leukemic stem cells (LSCs) are thought to be the main drivers of relapse in Acute Myeloid Leukemia. LSCs ability to retain key properties of healthy hematopoietic stem cells (HSCs) means they are quiescent, chemo-resistant, and able to repopulate eradicated leukemic blasts, making LSCs an important target in AML. However, their interactions with and regulation by the bone marrow microenvironment deserve further exploration. Here, we examined the efficacy of the megakaryocyte-derived chemokine platelet factor 4 (PF4) to inhibit LSC proliferation and alter the course of AML disease progression in syngeneic mouse models and human AML cells. We found that PF4 preferentially acts on LSCs via low-density lipoprotein receptor (LDLR) to inhibit their proliferation and deregulate lipid metabolism. When given in combination with chemotherapy, PF4 prolongs the overall survival of leukemic mice. Collectively, our results indicate that PF4 disrupts lipid metabolism in AML, halting disease progression and conferring long-term survival in leukemic mice.