High-Risk Multiple Myeloma: Distinguishing Early Failures from Sustained Control
High-Risk Multiple Myeloma: Distinguishing Early Failures from Sustained Control
High-Risk Multiple Myeloma: Distinguishing Early Failures from Sustained Control
High-Risk Multiple Myeloma: Distinguishing Early Failures from Sustained Control
High-Risk Multiple Myeloma: Distinguishing Early Failures from Sustained Control
High-Risk Multiple Myeloma: Distinguishing Early Failures from Sustained Control
High-Risk Multiple Myeloma: Distinguishing Early Failures from Sustained Control
High-Risk Multiple Myeloma: Distinguishing Early Failures from Sustained Control
High-Risk Multiple Myeloma: Distinguishing Early Failures from Sustained Control
High-Risk Multiple Myeloma: Distinguishing Early Failures from Sustained Control
High-Risk Multiple Myeloma: Distinguishing Early Failures from Sustained Control
High-Risk Multiple Myeloma: Distinguishing Early Failures from Sustained Control
High-Risk Multiple Myeloma: Distinguishing Early Failures from Sustained Control
High-Risk Multiple Myeloma: Distinguishing Early Failures from Sustained Control
High-Risk Multiple Myeloma: Distinguishing Early Failures from Sustained Control
High-Risk Multiple Myeloma: Distinguishing Early Failures from Sustained Control
High-Risk Multiple Myeloma: Distinguishing Early Failures from Sustained Control
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High-Risk Multiple Myeloma: Distinguishing Early Failures from Sustained Control

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Presented at annual meeting of ASCO (American Society of Clinical Oncology), held in Chicago June 4-8, 2010.

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  • NOTES: No genes overlapping with GEP70. Note high correlation of genes within each group PMAIP1/NOXA may define unique disease subset; NOXA targets MCL1, a 1q21 candidate gene, for proteasomal degradation; is VEL contraindicated; Note: MYB also removed/neutralized by proteasomal degradation PLK interacts with EVI5 a low 19 in GEP70 mapping to 1p22; high PLK might cooperate with del1p TP53INP1 regulated by TP53; high denovo TP53INP1 points to active TP53 in SC or cure fraction MAN2A1 and ST6GAL in EF point to loss of N-glycan biosynthesis; This is supported by MS proteomics SHISA, a Wnt suppressor that sequesters Frizzled in ER, acts similar to DKK1, which sequesters LRP5 by removal from PM SPIB induces plasmacytoid-dendritic cell differentiation; does this mean EF disease is pDC?; Wnt regulates keratinocyte differentiation/pDC like; are these are these pDC? MM can make dendritic processes, especially in MMCL; Lenalidomide induces RUNX2 is an osteoblast marker and FITM2 is an adipocyte marker; Ultra high risk is RUNX-positive OB-like
  • If high expression is good then it stands to reason that upregulation following short term PGx should be good too! Is a a) baseline, b) post drug, or c) change in TP53INP1 expression related to outcome? If not, such a link might be masked, e,g, they are GEP70 dependent? Subtype specific? delTp53 dependent? MDM2 and TP53 status? TP53INP1 is ROS activated (Ref). This may explain important role of ROS inducers, i.e. IMiDs in Mel-based ASCT? Does upregulation or lack thereof reflect degree of endogenous ROS? Can another type of drug, i.e. lenalidomide, which is a potent inducer of ROS, activate TP53INP1 to a greater degree and especially lift those disease entities exhibiting negligible change in response to Vel-Mel PGx challenge? Differentiate GEP signatures of those that do VERSUS those that don’t activate TP53INP1 following Vel-Mel ? And then compare such results to Len-Mel If hypotheses hold up, we will consider such to be strong rationale for ”HIGH DOSE LENALIDOMIDE IN COMBO WITH HIGH DOSE MEL” Does prior Velcade alter/influence Mel-induced changes seen here? IF true, does this shed light on Vel-Mel synergy, which is purported to be related to DNA repair pathway? IF true is this related to the improved outcome in TT3 v TT2? Reduction in expression tends to occur in the 20% with. One could hypothesize that the reduction is due to treatment induced apoptosis in a TP53INP1 HIGH population. This could be true for all cases where there is a reduction after treatment. Do we see similar changes in BX?
  • If high expression is good then it stands to reason that upregulation following short term PGx should be good too! Is a a) baseline, b) post drug, or c) change in TP53INP1 expression related to outcome? If not, such a link might be masked, e,g, they are GEP70 dependent? Subtype specific? delTp53 dependent? MDM2 and TP53 status? TP53INP1 is ROS activated (Ref). This may explain important role of ROS inducers, i.e. IMiDs in Mel-based ASCT? Does upregulation or lack thereof reflect degree of endogenous ROS? Can another type of drug, i.e. lenalidomide, which is a potent inducer of ROS, activate TP53INP1 to a greater degree and especially lift those disease entities exhibiting negligible change in response to Vel-Mel PGx challenge? Differentiate GEP signatures of those that do VERSUS those that don’t activate TP53INP1 following Vel-Mel ? And then compare such results to Len-Mel If hypotheses hold up, we will consider such to be strong rationale for ”HIGH DOSE LENALIDOMIDE IN COMBO WITH HIGH DOSE MEL” Does prior Velcade alter/influence Mel-induced changes seen here? IF true, does this shed light on Vel-Mel synergy, which is purported to be related to DNA repair pathway? IF true is this related to the improved outcome in TT3 v TT2? Reduction in expression tends to occur in the 20% with. One could hypothesize that the reduction is due to treatment induced apoptosis in a TP53INP1 HIGH population. This could be true for all cases where there is a reduction after treatment. Do we see similar changes in BX?
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