IGF1 and obesity due to melanocortin 4 receptor deficiency: 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.