INTERLEUKIN-15 PROMOTES THE GROWTH OF LEUKEMIC-CELLS OF PATIENTS WITHB-CELL CHRONIC LYMPHOPROLIFERATIVE DISORDERS

The recently discovered cytokine, interleukin-15 (IL-15), has been dem onstrated to share several biologic properties with IL-2 in different cell systems, including T-cell and natural killer (NK) cell compartmen ts. As for B lymphocytes, IL-15 has been shown to provide stimulatory activities in normal preactivated B cells that are mainly transduced t hrough IL-2 receptor (IL-2R) complex components. Since leukemic B cell s from patients with chronic lymphoproliferative disorders (CLD) bear IL-2R and grow in response to IL-2, we investigated whether IL-15 trig gers the proliferation of malignant B cells obtained from 12 patients with B-cell chronic lymphocytic leukemia (B-CLL) and five patients wit h hairy cell leukemia (HCL). Enriched B cells recovered from five heal thy subjects were also studied as controls. IL-15 stimulated the proli feration of freshly isolated leukemic B cells, but not resting normal B lymphocytes, the latter being able to grow in the presence of IL-15 only after in vitro preactivation with phorbol myristate acetate. The proliferation elicited by IL-2 on leukemic cells was comparable to tha t determined by IL-15, Following addition of graded concentrations of IL-15 to low/intermediate-dose IL-2, resting leukemic B cells showed a higher stimulatory rate than that observed using the two cytokines se parately. In normal resting B lymphocytes, this cumulative effect was not observed. The role of different IL-2R subunits in IL-15-driven gro wth of malignant B cells was investigated both by their expression on leukemic cells and by the block of different IL-2R subunits (p55, p75, and p64) with specific monoclonal antibodies (MoAbs). Using flow cyto metry and reverse transcriptase-polymerase chain reaction (RT-PCR) ana lyses we demonstrated that both B-CLL and HCL leukemic B cells express the beta and gamma chains of the IL-2R system. The stimulatory activi ty achieved by IL-15 decreased significantly, blocking the beta and ga mma chains of the IL-2R. Taken together, these findings demonstrate th at IL-15 triggers the growth of leukemic B cells through IL-2R system subunits, pointing to the role of this novel cytokine in regulating th e neoplastic proliferation in CLD. (C) 1996 by The American Society of Hematology.