ncRNA basic information ncRNA ID: MI0000479 ncRNA Database: miRBase ncRNA Name: miR-150 ncRNA Type: miRNA ncRNA Expression: down-regulated ncRNA Method: RT-qPCR ncRNA Target Gene: NA ncRNA Pathway: NA Evidence (ncRNA-drug): validated

drug basic information Drug ID: DB00619 (APRD01028, EXPT02967, DB03261) Drug Name: Imatinib Drug Method: In this study, we placed these findings into the broader context of the MYC/miR-150/MYB/miR-155/PU.1 oncogenic network. We propose that up-regulated MYC and miR-155 in CD34+ leukemic stem and progenitor cells, in concert with BCR-ABL1, impair the molecular mechanisms of myeloid differentiation associated with low miR-150 and PU.1 levels. We revealed that MYC directly occupied the -11.7 kb and -0.35 kb regulatory regions in the MIR150 gene. MYC occupancy was markedly increased through BCR-ABL1 activity, causing inhibition of MIR150 gene expression in CML CD34+ and CD34- cells. Furthermore, we found an association between reduced miR-150 levels in CML blast cells and their resistance to tyrosine kinase inhibitors (TKIs). Although TKIs successfully disrupted BCR-ABL1 kinase activity in proliferating CML cells, this treatment did not efficiently target quiescent leukemic stem cells. The study presents new evidence regarding the MYC/miR-150/MYB/miR-155/PU.1 leukemic network established by aberrant BCR-ABL1 activity. The key connecting nodes of this network may serve as potential druggable targets to overcome resistance of CML stem and progenitor cells. Drug Response: resistant

Cancer basic information Cancer: chronic myeloid leukemia Tissue/Cell: cell line (K562, MEG-01, KCL-22,HL-60 and KG-1)

Other information Title: BCR-ABL1 mediated miR-150 downregulation through MYC contributed to myeloid differentiation block and drug resistance in chronic myeloid leukemia. Journal: Haematologica Published: 2018 PubMed ID: 30049824