Dysregulation of IL-32 in myelodysplastic syndrome and chronic myelomonocytic leukemia modulates apoptosis and impairs NK function

• DOI: 10.1073/pnas.0712391105
• Publication Date: 2008-02-20T04:33:56Z
• Authors: A. Mario Marcondes; Andrew J. Mhyre; Derek L. Stirewalt; Soo-Hyun Kim; Charles A. Dinarello; H. Joachim Deeg
• Keywords: Chronic myelomonocytic leukemia

TNFα levels are elevated in the marrows of patients with myelodysplastic syndrome (MDS) and associated high rates apoptosis, which contributes to hematopoietic failure. We observed that exposure human marrow stroma cell lines HS5 HS27a increases IL-32 mRNA. IL-32, turn, induces TNFα. Marrow from MDS expressed 14- 17-fold higher mRNA than healthy controls. In contrast, cells chronic myelomonocytic leukemia (CMML) only one tenth level measured Human KG1a underwent apoptosis when cocultured stromal cells, but knockdown by using siRNA abrogated cells. also showed dysregulation VEGF other cytokines. Furthermore, CD56 + natural killer CMML at lower controls exhibited reduced cytotoxic activity, was unaffected IL-2 treatment. propose is a marker distinguishes CMML. appears contribute pathophysiology may be therapeutic target.