CALR and myeloproliferative disorder: Constitutive activation of the JAK-STAT signaling is the hallmark of all MPN and is sustained by somatic mutations in driver genes including JAK2, MPL, and CALR. The JAK-STAT pathway is critically involved in the regulation of cytokine- and growth factor receptor-mediated effects, as well as cell growth, survival, and differentiation of hematopoietic and immune compartments.