Leprosy drug clofazimine activates peroxisome proliferator-activated receptor- γ and synergizes with imatinib to inhibit chronic myeloid leukemia cells.

Leprosy drug clofazimine activates peroxisome proliferator-activated receptor-γ and synergizes with imatinib to inhibit chronic myeloid leukemia cells. Haematologica. 2019 Aug 01;: Authors: Kumar H, Chattopadhyay S, Das N, Shree S, Patel D, Mohapatra J, Gurjar A, Kushwaha S, Singh AK, Dubey S, Lata K, Kushwaha R, Mohammed R, Ghosh Dastidar K, Yadav N, Vishwakarma AL, Gayen JR, Bandyopadhyay S, Chatterjee A, Jain MR, Tripathi AK, Trivedi AK, Chattopadhyay N, Ramachandran R, Sanyal S Abstract Leukemia stem cells contribute to drug-resistance and relapse in chronic myeloid leukemia and BCR-ABL1 inhibitor monotherapy fails to eliminate them, thereby necessitating alternate therapeutic strategies. Peroxisome proliferator-activated receptor-γ (PPARγ) agonist pioglitazone downregulates signal transducer and activator of transcription 5 (STAT5) and in combination with imatinib induces complete molecular response in imatinib-refractory patients by eroding leukemia stem cells. Thiazolidinediones like pioglitazone however, are associated with severe side effects. To identify alternate therapeutic strategies for chronic myeloid leukemia we screened FDA-approved drugs in K562 cells and identified the leprosy drug clofazimine as an inhibitor of viability. Here we show that clofazimine induces apoptosis in chronic myeloid leukemia patient-derived blood mononuclear cells, with particularly robust effect in imatinib-resistant cells. Clofazimine al...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research