This particular role of IRS as effectors of versatile extracellular signals, which include not only insulin and IGF-1 but also interleukins (ILs) and other cytokines elevated in the systemic environment of chronic low-grade inflammation observed in obesity and insulin resistance, renders them and their related pathways key intersection points in the pathogenesis of leukemic disease in obesity. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.