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 also ind...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research

Related Links:

This study provides valuable experimental evidence for clinical MM therapy. PMID: 31538911 [PubMed - as supplied by publisher]
Source: Bosnian Journal of Basic Medical Sciences - Category: General Medicine Tags: Bosn J Basic Med Sci Source Type: research
Publication date: Available online 30 August 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Zuzan Cayci, Kerem Ozturk, Celalettin Ustun, Aazim K. Omer, Erhan Dincer, Zohar Sachs, Bruce A. Peterson, Michael A. LindenAbstractSarcoidosis has been shown to be associated with increased risk of development of several malignancies including lymphomas. On the other hand, “sarcoid-like reactions” in the absence of other clinical signs of sarcoidosis, have also been described in patients who had been treated with chemotherapy for a wide variety of malignancies. In this article, we report 3 cases who had PET...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Conference abstracts
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news
This study was aimed at detecting NRAS G12D and NRAS G13C mutant genes among apparently healthy and haematologic malignant individuals, and to explore their association with some clinical and demographic factors as well as disease status and progression. A total of 200 cfDNAs, 100 each from haematologic malignant patients and blood donors, respectively, were analyzed for the presence of NRAS gene mutations in codons 12 and 13. These mutations were tested using multiplex allele-specific PCR (AS-PCR). The mutations were detected by selective amplification using mutation-specific synthetic oligonucleotides. NRAS G12D and NRAS...
Source: Journal of Immunoassay and Immunochemistry - Category: Biochemistry Tags: J Immunoassay Immunochem Source Type: research
Conclusions: A Medication Event Monitoring System was applied for the direct evaluation of oral dasatinib adherence for the first time, and the clinical effect of dasatinib was investigated under the strict monitoring of patient adherence. Although this study had a small sample size, the plasma concentration monitoring of dasatinib is considered to be useful to predict an earlier molecular response with fewer edematous adverse events.
Source: Therapeutic Drug Monitoring - Category: Drugs & Pharmacology Tags: Original Article Source Type: research
This study investigated the effect of genetic variants in hepatocyte nuclear factor 4 alpha (HNF4α, encoded by gene NR2A1), a pivotal transcriptional regulator of drug disposition genes, on dose-adjusted IM-free plasma levels and related adverse reactions in Chinese GIST patients. Methods: Five common polymorphisms of NR2A1 (rs3818247, rs1884613, rs2071197, rs2425640, and rs736824) were genotyped in 70 Chinese GIST patients who had been administered IM 300–600 mg/d. The free IM trough plasma levels were determined based on a method of ultrafiltration coupled with high performance liquid chromatography-tandem...
Source: Therapeutic Drug Monitoring - Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Conclusions: Collectively, given its sensitivity with low cell numbers and avoidance of radioactive substrates, UHPLC-MS/MS–based analysis of FPGS activity may be eligible for routine therapeutic drug monitoring of MTX in RA and leukemia for therapy (non)response evaluations.
Source: Therapeutic Drug Monitoring - Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Conclusions: Tacrolimus therapeutic drug monitoring improved treatment outcomes of Chinese alloHSCT recipients. Cv measurements during weeks 3–4 and C0 or C2 measurements during weeks 5–6 better predicted aGVHD (I–IV) than the concentrations measured at other time points during the first 6 weeks after alloHSCT.
Source: Therapeutic Drug Monitoring - Category: Drugs & Pharmacology Tags: Original Article Source Type: research
Publication date: Available online 2 August 2019Source: BurnsAuthor(s): Jae Hyek Choi, Corina Necsoiu, Daniel Wendorff, Bryan Jordan, Alexander Dixon, Teryn R. Roberts, Brendan M. Beely, Leopoldo C. Cancio, Andriy I. BatchinskyAbstractBackgroundWe investigated effects of mesenchymal stem cells (MSC) or low-flow extracorporeal life support (ECLS) as forms of adjunct treatment for acute respiratory distress syndrome (ARDS) due to smoke inhalation injury (SII) and 40% TBSA burns by assessing their effects on histological injury scores. We hypothesized that adjunct treatments decrease histological end-organ damage.MethodsAnest...
Source: Burns - Category: Dermatology Source Type: research
Conclusions: The abnormal location of FLT3 caused by different glycosylation status leads to the distinguishing signaling pathways. Targeting on FLT3 glycosylation may provide a new perspective for therapeutic strategies. Abbreviations: ABCG2: ATP-binding cassette transporter breast cancer resistance protein; ATF: activating transcription factor; AML: acute myeloid leukemia; CHOP: CCAAT-enhancer-binding protein homologous protein; 2-DG: 2-deoxy-D-glucose; EFS: event free survival; EPO: erythropoietin; EPOR: erythropoietin receptor; ERS: endoplasmic reticulum stress; FLT3: FMS-like tyrosine kinase 3; GPI: glycosylphosphatid...
Source: Hematology - Category: Hematology Tags: Hematology Source Type: research
More News: Actos | Chronic Leukemia | Chronic Myeloid Leukaemia | Gleevec | Hematology | Leprosy | Leukemia | Stem Cell Therapy | Stem Cells | Study