High CXCR3 on Leukemic Cells Distinguishes [IgHV.sup.mut] from [IgHV.sup.unmut] in Chronic Lymphocytic Leukemia: Evidence from [CD5.sup.high] and [CD5.sup.low] Clones

Despite the shared pattern of surface antigens, neoplastic cells in chronic lymphocytic leukemia (CLL) are highly heterogeneous in CD5 expression, a marker linked to a proliferative pool of neoplastic cells. To further characterize [CD5.sup.high] and [CD5.sup.low] neoplastic cells, we assessed the chemokine receptors (CCR5, CCR7, CCR10, CXCR3, CXCR4, CXCR5) and adhesion molecules (CD54, CD62L, CD49d) on the [CD5.sup.high] and [CD5.sup.low] subpopulations, defined by CD5/CD19 coexpression, in peripheral blood of CLL patients (n = 60) subgrouped according to the IgHV mutational status ([IgHV.sup.mut], n = 24; [IgHVn.sup.mut], n = 36). [CD5.sup.high] subpopulation showed a high percentage of CXCR3 (P < 0.001), CCR10 (P = 0.001), and CD62L (P = 0.031) and high levels of CXCR5 (P = 0.005), CCR7 (P = 0.013) compared to [CD5.sup.low] cells expressing high CXCR4 (P < 0.001). Comparing [IgHV.sup.mut] and [IgHV.sup.unmut] patients, high levels of CXCR3 on [CD5.sup.high] and [CD5.sup.low] subpopulations were detected in the [IgHV.sup.mut] patients, with better discrimination in [CD5.sup.low] subpopulation. Levels of CXCR3 on [CD5.sup.low] subpopulation were associated with time to the next treatment, thus further confirming its prognostic value. Taken together, our analysis revealed higher CXCR3 expression on both [CD5.sup.high] and [CD5.sup.low] neoplastic cells in [IgHV.sup.mut] with a better prognosis compared to [IgHV.sup.unmut] patients. Contribution of CXCR3 to CLL pathophysiology and its suitability for prognostication and therapeutic exploitation deserves future investigations.