Sl-401, A Targeted Therapy Directed To The Interleukin-3 Receptor (Il-3r), Shows Cytotoxic Activity Against Hairy Cell Leukemia

Background: Hairy cell leukemia (HCL) is a rare B-lymphocyte disorder that is characterized by abnormal lymphoproliferation, cytoplasmic villous “hairy” projections, and infiltration of the bone marrow and spleen. These cellular changes lead to peripheral cytopenia and splenomegaly. HCL cases comprise approximately 2% of all leukemias, with an incidence of approximately 600-800 and prevalence of approximately 6,000 cases annually in the U.S. The purine analogs Leustatin® (cladribine) and Nipent® (pentostatin) induce high complete remission (CR) rates (70-95%), with most patients remaining in CR after 10+ years. However, there is an increasing number of patients who either relapse or become refractory to each successive purine analog therapy given, and for these patients there are currently no approved therapies. Since HCL is known to express high levels of the interleukin-3 receptor (IL-3R) α-chain (CD123), we tested the cytotoxic activity of SL-401, a novel targeted therapy directed to CD123, against HCL cells.