Others proved that miR 150 expression increases during B lymphoid differentiation in contrast to myeloid differentiation. It seems likely that miR 150 regulates the development of other two different blood lineages. B lymphocytes and megakaryocytes. Thus, miR 150 deregulation is found in hematological malignancies. miR 150 is decreased in polycytemia vera reticulocytes and a marked sellckchem decrease was recently also detected in MDS del while, in contrast, a twofold Inhibitors,Modulators,Libraries increase was found in CLL lymphocytes. Based on our results and recent results of others we expanded real time qPCR assays of miR 150 on the larger cohort of CML patients. Decreased level of miR 150 was confirmed in patients at diagnosis, in the majority of patients with hematological relapse and in accelerated phase and blast crisis.

Normal miR 150 level was observed in imatinib treated patients with major molecular response and failure to achieve CCgR. Our observations Inhibitors,Modulators,Libraries are consistent with the data of Flamant et al. showing rapid increase of miR 150 expression after imatinib treatment initiation in patients with newly diagnosed CML. They further found that low miR 150 expression inversely Inhibitors,Modulators,Libraries correlated with white blood count and thus speculated that the level reflected the high leu kocyte counts in newly diagnosed CML patients. We showed here a significant inverse correlation of miR 150 expression with BCR ABL transcript level. Non treated newly diagnosed patients, patients with disease progression and resistant to imatinib showed a high level of BCR ABL together with high leu kocyte count and decreased amount of miR 150.

Normal miR 150 level was detected in imatinib responders and patients with failure to achieve CCgR with normal blood count and low BCR ABL transcript level. As imatinib targets Ph cells, the normal level of miR 150 in imatinib treated patients in chronic phase with physiological blood count could be the Inhibitors,Modulators,Libraries result of the suppression of leukemic cells and the concomitant recovery of normal hematopoiesis under imatinib treat ment. Our in vitro tests showed elevated expression of miR 150 and marked decrease of p CRKL following imatinib in vitro treatment of Ph cell line Inhibitors,Modulators,Libraries MOLM 7. These findings suggest a potential functional relation ship between miR 150 and BCR ABL. Gene expression of MYB in our study showed a signif icant inverse correlation with miR 150 transcript level.

MYB is the proven target of miR 150 and encodes a transcriptional factor required for prolif eration and survival of normal and leukemic blast cells. A recently published study on a mouse model of blast crisis reported that c MYB is required for BCR ABL dependent selleck compound leukemogenesis. Lidonnici et al. speculated that miR 150 reduction might contribute to the c MYB upregulation that is likely induced by BCR ABL, and may be involved in BCR ABL driven leukemo genesis in CML.