In summary, the present findings demonstrate that a strategy combining Chk1 with MEK1/2 inhibitors is shows pronounced activity against MM cells with acquired bortezomib-resistance or ectopically expressing high levels of Mcl-1, an anti-apoptotic protein which has been implicated in resistance to numerous anti-MM agents including bortezomib [8], [9] as well as in drug resistance conferred by microenvironmental factors [15], [48]. This evidence concerns the gene MAP2K1 and Miyoshi myopathy.