The ibrutinib B-cell proliferation inhibition is potentiated in vitro by dexamethasone: Application to chronic lymphocytic leukemia

Autor: Régine Catallo, Anne-Sophie Michallet, Olivier Roualdes, Jean-Pierre Magaud, Lucile Baseggio, Amel Chebel, Martine Ffrench, Gilles Salles, Delphine Manzoni
Přispěvatelé: Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Cancer Research
Chronic lymphocytic leukemia
Apoptosis
Pharmacology
Dexamethasone
[ SDV.CAN ] Life Sciences [q-bio]/Cancer
chemistry.chemical_compound
0302 clinical medicine
Piperidines
Tumor Cells
Cultured
Lymphocytes
Aged
80 and over
B-Lymphocytes
Leukemia
biology
Cell Cycle
Drug Synergism
Hematology
Cell cycle
Middle Aged
3. Good health
Oncology
030220 oncology & carcinogenesis
Ibrutinib
Female
France
Antineoplastic Agents
Hormonal
Patients
Cells
[SDV.CAN]Life Sciences [q-bio]/Cancer
03 medical and health sciences
Cyclin-dependent kinase
Stress
Physiological
medicine
Bruton's tyrosine kinase
Humans
Aged
Cell Proliferation
therapy
Cell growth
business.industry
Adenine
Proteins
Dna
medicine.disease
Leukemia
Lymphocytic
Chronic
B-Cell
030104 developmental biology
Pyrimidines
chemistry
biology.protein
Pyrazoles
pathology
business
Laboratories
DNA Damage
Zdroj: Leukemia Research
Leukemia Research, 2016, 47, pp.1--7. 〈10.1016/j.leukres.2016.05.003〉
Leukemia Research, Elsevier, 2016, 47, pp.1--7. ⟨10.1016/j.leukres.2016.05.003⟩
ISSN: 0145-2126
DOI: 10.1016/j.leukres.2016.05.003〉
Popis: International audience; New B-cell receptor-targeted therapies such as ibrutinib, a Bruton tyrosine kinase inhibitor, are now proposed for lymphoid pathologies. The putative benefits of its combination with glucocorticoids were evaluated here. We compared the effects of dexamethasone (DXM), ibrutinib and their in vitro combination on proliferation and metabolic stress markers in stimulated normal B-lymphocytes and in malignant lymphocytes from chronic lymphocytic leukemia (CLL) patients. In both cellular models, cell cycle progression was globally inhibited by DXM and/or ibrutinib. This inhibition was significantly amplified by DXM addition to ibrutinib and was related to a significant decrease in the expression of the cell cycle regulatory proteins CDK4 and cyclin E. Apoptosis increased especially with DXM/ibrutinib combination and was associated with a significant decrease in Mcl-1 expression. Treatment effects on metabolic stress were evaluated by DNA damage recognition after 53BP1 foci labeling. The percentage of cells with more than five 53BP1 foci decreased significantly with ibrutinib in normal and CLL lymphocytes. This decrease was strongly reinforced, in CLL, by DXM addition. Our data indicated that, in vitro, DXM potentiated antiproliferative effects of ibrutinib and decreased DNA damage in lymphoid B-cells. Thus their combination may be proposed for CLL treatment
Databáze: OpenAIRE
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