Role of IL8 in myeloid malignancies.

ABSTRACT

Aberrant overexpression of Interleukin-8 (IL8) has been reported in Myelodysplastic Syndromes (MDS), Acute Myeloid Leukemia (AML), Myeloproliferative Neoplasms (MPNs) and other myeloid malignancies. IL8 (CXCL8) is a CXC chemokine that is secreted by aberrant hematopoietic stem and progenitors as well as other cells in the tumor microenvironment. IL8 can bind to CXCR1/CXCR2 receptors and activate oncogenic signaling pathways, and also increase the recruitment of myeloid derived suppressor cells to the tumor microenvironment. IL8/CXCR1/2 overexpression has been associated with poorer prognosis in MDS and AML and increased bone marrow fibrosis in Myelofibrosis. Preclinical studies have demonstrated benefit of inhibiting the IL8/CXCR1/2 pathways via restricting the growth of leukemic stem cells as well as normalizing the immunosuppressive microenvironment in tumors. Targeting the IL8-CXCR1/2 pathway is a potential therapeutic strategy in myeloid neoplasms and is being evaluated with small molecule inhibitors as well as monoclonal antibodies in ongoing clinical trials. We review the role of IL8 signaling pathway in myeloid cancers and discuss future directions on therapeutic targeting of IL8 in these diseases.