Activation of the Mtor Signaling Pathway in Multiple Myeloma Patients and Its Prognostic Significance.

INTRODUCTION The mammalian target of rapamycin (mTOR) is a serine/threonine-specific protein kinase, downstream of the phoshatidylinositol 3-kinase (P13K)/AKT pathway. It controls many aspects of cellular physiology, including transcription, translation, cell size, cytosckeletal organization, autophagy and progression from the G1 to S phase of the cell cycle. Constitutive activation of the mTOR related downstream effectors including P13K, AKT, p70S6K and 4EPB1 was found in numerous malignancies. Rapamycin and its analogues are mTOR inhibitor currently being tested in solid and hematological tumours. Previous studies demonstrated that rapamycin have preclinical potential as therapy for multiple myeloma, especially when associated with other drugs. We first determined the frequency of the activation status of AKT/mTOR/p70S6K pathway in multiple myeloma patients and correlated its activation with FISH analysis and clinical data.