The Role of Leptin in Pathophysiology of Myeloma Cells

In order to achieve the best therapeutic strategy with which to treat multiple myeloma (MM), it is necessary to understand the molecular mechanisms of myeloma cell growth. In addition to genetic defects, the bone marrow microenvironment (BMM) plays a primary role in MM pathophysiology. For many years, interleukin-6 (IL-6) was considered to be a central growth factor in myeloma cells. However, recent evidence indicates that increasing numbers of cytokines enhance myeloma cell growth in BMM. In this study, we investigated the possibility that leptin could be a member of cytokine network that supports myeloma cells.

The expression of leptin and its receptors in cell lines, bone marrow (BM) and mononuclear peripheral blood (PB) were analysed by RT-PCR. Additionally, leptin serum levels were analysed by ELISA and the effect of leptin on growth of cell lines by cell culture.According to our results,leptin and its receptors were expressed in cell lines, myeloma BM and PB mononuclear cells (MNC). However the PB mononuclear cells of treated myeloma patients did not express leptin and differed in the expression of leptin receptors. Acute lymphoid leukemia, B-blasts (B-ALL) did not express leptin and its receptors. Untreated myeloma and B-ALL patients had high and low levels of leptin in their serum, respectively. Recombinant exogenous leptin enhanced the growth of RPMI8866 but did not affect the growth of U66 and Jurkat.Regarding this study and the findings of other studies, leptin may play a role in MM pathophysiology. Therefore leptin and its receptors might be analysed as a therapeutic target for myeloma BMM.