Hypoxia-induced p38 MAPK activation reduces Mcl-1 expression and facilitates sensitivity towards BH3 mimetics in chronic lymphocytic leukemia

Leukemia. 2015 Apr;29(4):981-4. doi: 10.1038/leu.2014.320. Epub 2014 Nov 7.

Authors

M F Huelsemann¹, M Patz¹, L Beckmann¹, K Brinkmann², T Otto³, J Fandrey³, H J Becker⁴, S Theurich⁴, M von Bergwelt-Baildon⁴, C P Pallasch¹, R P Zahedi⁵, H Kashkar², H C Reinhardt¹, M Hallek¹, C M Wendtner⁶, L P Frenzel¹

Affiliations

¹ 1] Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany [2] Center of Integrated Oncology, University Hospital of Cologne, Cologne, Germany [3] Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University Hospital of Cologne, Cologne, Germany.
² 1] Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University Hospital of Cologne, Cologne, Germany [2] Institute for Medical Microbiology, Immunology and Hygiene, University Hospital of Cologne, Cologne, Germany.
³ Institute of Physiology, University of Duisburg-Essen, Essen, Germany.
⁴ 1] Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany [2] Center of Integrated Oncology, University Hospital of Cologne, Cologne, Germany.
⁵ Leibniz-Institute for Analytical Sciences-ISAS-e.V., Dortmund, Germany.
⁶ 1] Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany [2] Center of Integrated Oncology, University Hospital of Cologne, Cologne, Germany [3] Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University Hospital of Cologne, Cologne, Germany [4] Department I of Internal Medicine, Klinikum Schwabing, Munich, Germany.

PMID: 25376373
DOI: 10.1038/leu.2014.320

No abstract available

Publication types

Letter
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology*
B-Lymphocytes / drug effects*
B-Lymphocytes / metabolism
B-Lymphocytes / pathology
Bendamustine Hydrochloride
Biphenyl Compounds / pharmacology*
Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
CD40 Ligand / genetics
CD40 Ligand / metabolism
Cell Hypoxia
Cells, Cultured
Drug Resistance, Neoplasm
Enzyme Activation
Gene Expression Regulation, Leukemic*
Humans
Leukemia, Lymphocytic, Chronic, B-Cell / genetics
Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
Leukemia, Lymphocytic, Chronic, B-Cell / pathology
Myeloid Cell Leukemia Sequence 1 Protein / antagonists & inhibitors*
Myeloid Cell Leukemia Sequence 1 Protein / genetics
Myeloid Cell Leukemia Sequence 1 Protein / metabolism
Nitrogen Mustard Compounds / pharmacology
Nitrophenols / pharmacology*
Oxygen / pharmacology
Piperazines / pharmacology
Proto-Oncogene Proteins c-bcl-2 / genetics
Proto-Oncogene Proteins c-bcl-2 / metabolism
Signal Transduction
Sulfonamides / pharmacology*
Vidarabine / analogs & derivatives
Vidarabine / pharmacology
bcl-X Protein / genetics
bcl-X Protein / metabolism
p38 Mitogen-Activated Protein Kinases / genetics*
p38 Mitogen-Activated Protein Kinases / metabolism

Substances

ABT-737
Antineoplastic Agents
BCL2 protein, human
Biphenyl Compounds
Bridged Bicyclo Compounds, Heterocyclic
MCL1 protein, human
Myeloid Cell Leukemia Sequence 1 Protein
Nitrogen Mustard Compounds
Nitrophenols
Piperazines
Proto-Oncogene Proteins c-bcl-2
Sulfonamides
bcl-X Protein
CD40 Ligand
Bendamustine Hydrochloride
p38 Mitogen-Activated Protein Kinases
Vidarabine
venetoclax
fludarabine
Oxygen