ENAGenomicsMultiomicsMedicine, University of Colorado, Denverhttps://www.ebi.ac.uk/ena/browser/view/PRJNA125995Homo sapiensxref:PubMed:20609354Although Bcr-Abl kinase inhibitors have proven effective in the treatment of chronic myeloid leukemia (CML), they generally fail to completely eradicate Bcr-Abl+ leukemia cells. To identify genes whose inhibition sensitizes Bcr-Abl+ leukemias to killing by Bcr-Abl inhibitors, we performed an RNAi-based synthetic lethal screen with imatinib in CML cells. This screen identified numerous components of a Wnt/Ca2+/NFAT signaling pathway. Antagonism of this pathway led to impaired NFAT activity, decreased cytokine production and enhanced sensitivity to Bcr-Abl inhibition. Furthermore, NFAT inhibition with cyclosporin A facilitated leukemia cell elimination by the Bcr-Abl inhibitor dasatinib and markedly improved survival in a mouse model of Bcr-Abl+ acute lymphoblastic leukemia (ALL). Targeting this pathway in combination with Bcr-Abl inhibition could improve treatment of Bcr-Abl+ leukemias. Overall design: We utilized a genome-wide shRNA library in combination with microarray analysis to screen for gene targets in chronic myeloid leukemia cells that cooperate with imatinib.ENAv-abl, Dmel_CG00000, Dm DWnt3/5, DWnt-5, DWnt-4, Ableson, Dint-1, DmelCG4889, abl1, AblK., 5133400C09Rik, apolipoprotein B deficiency, Bassen Kornzweig syndrome, l(2)wg, acanthocytosis, DWnt-3/5, l(3)04674, CML, wnt-4, cAbl, CG17617, C-abl, int-1, Ca2+, Bassen-Kornzweig syndrome, Dm-1, Dm-2, Nfat, Dm-3, p150, DmelCG1916, leukaemia NOS, BCR, rhoGAP1A, CG40494, congenital betalipoprotein deficiency syndrome, JTK7, Leucocythaemia, Dm Wg, Wnt-4, leukaemia, l(2)02657, Wnt-1, Wnt-3, Wnt-2, BCR1, DmelCG40494, AI325092, I, dAbl, DmelCG6407, Abl, CALCIUM ION, ABL, D22S11, Leucocythemias, PHL, dWnt, EG:23E12.5, Abl1, DWnt5, Wnt/Wg, Wnt, DWnt4, WNT, DWnt3, Wnt1, EG:23E12.2, DWnt2, Wnt3, microsomal triglyceride transfer Protein deficiency, wnt4, wnt3, wnt2, AI853148, wnt1, Wnt3/5, DmelCG4698, c-Abl, c-ABL, Dwnt5, CG4032, abl, time of survival, Dwnt4, wnt5, Br, dWnt2, wnt, Sp, single organism signaling, E430008G22Rik, leukemia, ALL, Betalipoprotein deficiency disease, Dabl, c-abl, l(2)rO727, Am ABL, D-Abl, Dash, l(3)73Ba, DAbl, wgl, Leukemias, Cell, doubly charged positive ion, D22S662, spd, survival, clone 2.4, D-wnt-2, CG40453, D-abl, DWint-1, D-ash, CG4889, DmelCG4032, Leucocythaemias, AI561783, DWnt3/5, fg, bcr/abl, NF-AT5, Leucocythemia, l(3)c-abl, 4674, death rate, anon-WO03040301.228, MTP deficiency, anon-EST:Liang-2.4, CG4698, WG, bcr|abl, Dwnt-2, Dwnt-3, Ca(2+), Dm DWnt2, CG17960, Dm DWnt4, Ddash/abl, calcium, Dsrc7, CG1916, TonEBP, signalling process, Dwnt-5, Wg, DROTKABL3, mKIAA3017, DWnt-3, c-ABL1, DWnt-2, abetalipoproteinemia neuropathy, DWnt-1, Gla, CG6407Human, Modern., human being, Man (Taxonomy), Homo sapiens, man, Man, human, Modern ManfalseHomo sapiensWnt/Ca2+/NFAT signaling maintains survival of Ph+ leukemia cells upon inhibition of Bcr-Abl2025-09-242014-02-11PRJNA125995GSE21499960620609354