Abnormal JAK2 activation has been implicated in several hematological disorders and malignancies. Mutations, gene translocations or cytokines released by bone marrow stromal cells, may all result in aberrant JAK2 activation. The activating JAK2 V617F mutation results in uncontrolled cytokine and growth factor signaling, and is believed to play a key role in the pathophysiology of myeloproliferative neoplasms. Constitutive JAK2 activation through specific chromosomal translocations is thought to contribute to the development of leukemia, lymphoma and multiple myeloma. In MM, elevated levels of cytokines and growth factors such as interleukin-6 (IL 6), vascular endothelial growth factor, insulin-like growth factor-1, basic fibroblast growth factor, IL-1, IL-10, IL-11, IL-15, IL-21, granulocyte macrophage colony stimulation factor, interferon-α, and leukemia inhibitory factor may also contribute to exacerbated JAK2 activation.11 Among these cytokines, IL-6 has been most widely studied and is considered to be a growth and survival factor for myeloma cells. Binding of IL-6 to the IL-6 receptor activates JAK2, which in turn can phosphorylate the IL-6 receptor, thereby augmenting its downstream signaling effects. Thus, pharmacological inhibition of JAK1/2 may be a promising therapeutic strategy for treatment of MM.