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Analysis of the Metabolic State of Residual Multiple Myeloma Plasma Cells Reveals a Proliferative Subset with Glycolytic Gene Expression

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 Most residual MMPCs have lower ROS and higher superoxide and mitochondrial content.  A subset of residual cases had higher ROS levels along with elevated Myc, HK2, CD147 and… Click to show full abstract

 Most residual MMPCs have lower ROS and higher superoxide and mitochondrial content.  A subset of residual cases had higher ROS levels along with elevated Myc, HK2, CD147 and reduced POU2F1 expression, possibly indicating loss of dormancy and transition to active disease  Metabolic characteristics of residual disease were recapitulated in galactose-conditioned MMCLs and had reduced Myc, HK2 and CD147 expression and reduced glucose uptake. After Myc inhibition, these parameters were also reduced in MMCLs cultured in standard glucose-containing medium.  We developed a metabolic score to detect increased glycolytic and proliferative activity and found that it increases with disease stage.  The metabolic score will be used for precision targeting of residual MMPCs with antimetabolic drugs and to examine efficacy of predicting progression of residual MM cases based on metabolic changes in prospective studies.  Detected by FACS:  In WBM of primary samples:  ROS (H2DCFDA),  superoxide (DHE)  mitochondrial content (Mitotracker)  In MMCLs:  CD147  Glucose uptake (NBDG)

Keywords: analysis metabolic; residual multiple; multiple myeloma; metabolic state; expression; state residual

Journal Title: Blood
Year Published: 2017

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