CML is the most common myeloproliferative disease observed among adults, its 1st line of treatment is IM with a response rate ranging between 55 - 90%. In Qatar the resistance rate is higher than 45%. Our collaborators in Italy recently reported on the relation between CML and PTPRG.Our team reported previously on the high rate of resistance of CML to IM (45%). During this forum the team is further reporting on the possible underlying mechanisms behind this resistance (see Al-Dewik et al at this forum).Despite a few positive findings, no pattern could be identified to delineate a significant underlying mechanism. Our collaborators in Italy, identified that down-regulation of PTPRG increased colony formation in the PTPRG+ve megakaryocytic MEG-01 and LAMA-84, but had no effect in the PTPRG-ve K562 and KYO-1. Its over-expression had an oncosuppressive effect in all four cell lines and is associated with inhibition of BCR/ABL-dependent signalling. PTPRG was downregulated at the mRNA and protein levels in CML patients in both PB and BM, including CD34+ cells, and is re-expressed following molecular remission of disease. This re-expression was associated with loss of methylation of a CpG island of PTPRG promoter in 55% patients. In K562 cells, the hypomethylating agent 5-aza-2’-deoxycytidine induced PTPRG expression and caused inhibition of colony formation that was partially reverted by antisense-mediated downregulation of PTPRG expression. Conclusions: Although this study was done on 2 independent patient populations, it suggests that in CML populations with high resistance rate it might be worth examining the PTPRG expression level and correlate it with the pattern of resistance. Our group has secured 3 years funding from QNRF (NPRP 4-157-3-052) to investigate PTPRG signalling in CML, including the study of a possible link among the high CML resistance and the PTPRG expression levels.
High Resistance Rate of Chronic Myeloid Leukaemia (CML) to Imatinib Myselate (IM) Might be Related to Protein Tyrosine Phosphatase Receptor Type Gamma (PTPRG) Down-Regulation
MORATTI, Elisabetta;VEZZALINI, Marzia;SILVESTRI, Giovannino;Stradoni, Roberta Daniela;SORIO, Claudio
2011-01-01
Abstract
CML is the most common myeloproliferative disease observed among adults, its 1st line of treatment is IM with a response rate ranging between 55 - 90%. In Qatar the resistance rate is higher than 45%. Our collaborators in Italy recently reported on the relation between CML and PTPRG.Our team reported previously on the high rate of resistance of CML to IM (45%). During this forum the team is further reporting on the possible underlying mechanisms behind this resistance (see Al-Dewik et al at this forum).Despite a few positive findings, no pattern could be identified to delineate a significant underlying mechanism. Our collaborators in Italy, identified that down-regulation of PTPRG increased colony formation in the PTPRG+ve megakaryocytic MEG-01 and LAMA-84, but had no effect in the PTPRG-ve K562 and KYO-1. Its over-expression had an oncosuppressive effect in all four cell lines and is associated with inhibition of BCR/ABL-dependent signalling. PTPRG was downregulated at the mRNA and protein levels in CML patients in both PB and BM, including CD34+ cells, and is re-expressed following molecular remission of disease. This re-expression was associated with loss of methylation of a CpG island of PTPRG promoter in 55% patients. In K562 cells, the hypomethylating agent 5-aza-2’-deoxycytidine induced PTPRG expression and caused inhibition of colony formation that was partially reverted by antisense-mediated downregulation of PTPRG expression. Conclusions: Although this study was done on 2 independent patient populations, it suggests that in CML populations with high resistance rate it might be worth examining the PTPRG expression level and correlate it with the pattern of resistance. Our group has secured 3 years funding from QNRF (NPRP 4-157-3-052) to investigate PTPRG signalling in CML, including the study of a possible link among the high CML resistance and the PTPRG expression levels.
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