Abnormal expression of onkomir miR 17 92 was described in CML CD34 cells. Agirre et al. found up regulated miR 221 and Wortmannin price miR 222 in mononuclear cells of CML patients in comparison to healthy controls. MiR 155, miR 106a, miR 146a, miR 181 and miR 126 were reported as deregulated miRNAs in CML. To our knowledge, let7c expression has so far not been described in CML. In this study, our in silico analyses revealed that miR 221 and miR 103 target PIK3R1. PIK3R3 is predicted to be regulated by miR 19a and miR 181a. PI3K is annotated in ERBB, MAPK and mTOR signaling pathways. KRAS, which is involved in MAPK signaling, is a predicted target of miR 19a. MAPK expression may be regulated by onkomirs miR 17 and miR 19a. Interestingly, it was reported that RAS/MAPK signaling may contribute to the survival of BCR ABL positive cells under imatinib selection pressure.

Inhibitors,Modulators,Libraries AKT1, a member of the antiapoptotic PI3K pathway, is involved in both, BCR ABL mediated transformation as well as in response to the BCR ABL kinase inhibitors. It was shown that the PI3K/AKT/mTOR signaling is activated in imatinib naive cells while under imatinib pressure it may enhance resistance to imatinib. As shown in our real time qPCR data, the rather decreased levels of miR 181a, miR 221 and miR 19a in some ima tinib treated patients, and miR 103 down regulation in a number of blast crisis, diagnosis and progressed CML may contribute to the increased Inhibitors,Modulators,Libraries level of PI3K and thus may be involved in the previously described PI3K/AKT/ mTOR signaling activation and in the resistance devel opment in some CML cases.

Though no experimental therapy using miRNA modulation has as yet provided significant and curative approach, the knowledge of deregulation of miRNAs specific for CML may facilitate the development of such therapeutic strategies. Several candidate microRNAs regulating expression Inhibitors,Modulators,Libraries in CML target important signaling pathways may represent promising candidate targets Inhibitors,Modulators,Libraries for CML therapy. The real time qPCR validated the down regulation of miR 150, miR 451, miR 103 and miR 144 overall in individual samples of BC, Hr, Dg pools and in some samples of TF pool. These molecules may be related to the CML pathogenesis and may reflect trans formation from chronic to accelerated phases. Agirre et al. found miR 150 downregulation in mononuclear cells and CD34 cells separated from bone marrow in newly diagnosed CML patients in comparison to healthy donors.

MiR 150 was recently described to be downregulated in untreated CML patients. Flamant et al. suggest that miR 150 play a role in leukemic cells and potentially in the more primitive hematopoietic compartment in chronic phase CML patients. This Inhibitors,Modulators,Libraries is in line with add to favorites the knowledge that miR 150 is important in the regulation of hematopoiesis. During normal erythroid differentiation its level is gra dually decreased, however.