Growth in Juvenile Myelomonocytic Leukemia Cells1

Juvenile myelomonocyticleukemia (JMML)carries a poor prognosis. The endogenousproductionofcytokines by the JMMLcells contributesto their growth and therapeutic resistance. Interleukin (IL)-4, IL-lO, and IL-13 inhibit cytokine production in monocytes. We have now studied whether these cytokines can inhibit JMML cell cytokine production, thereby potentiallyreducingthe malignantcell load in this dIsorder.We found that IL-lO, but not IL-4 or IL-13, dose dependently inhibited JMML cell production of the hemopoietic growth factors granulocyte macrophagecolony-stimulatingfactor, tumor necrosis factor a, and IL 113.Similarly,IL-b, but not IL-4 or IL-13,suppressedJMML colony formation and cell viability. This was not due to the absence of receptors because we could detect mRNAs for the IL-4 and the IL-13 receptor a subunits and the IL-2 common y subunit in JMML cells. Furthermore, the receptorswere active since both IL-4 and IL-13 up-regulatedsurface expression of MHC class 11and down-regulated CD14 antigens on JMML cells and monocytes.Unlike activatedmonocytes,the JMMLcells did not produceIL-lO.It is suggestedthat the loss of cytokineinhibitoryeffectsof IL-4 and IL-13 could play a role in the pathogenesis of this disorder. On the other hand, the inhibitionof cytokineproduction,growth,and viabil ity of JMML cells by IL-lO suggests that this cytokine may have a therapeutic potential in JMML.