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Bruton's tyrosine kinase is at the crossroads of metabolic adaptation in primary malignant human lymphocytes.

ABSTRACT: In this work we explored metabolic aspects of human primary leukemic lymphocytes that hold a potential impact on the treatment of Bruton tyrosine kinase (BTK)-driven diseases. Our results suggest that there is crosstalk between Bruton tyrosine kinase (BTK) signaling and bioenergetic stress responses. In primary chronic lymphocytic leukemia (CLL) lymphocytes, pharmacological interference with mitochondrial ATP synthesis or glucose metabolism affects BTK activity. Conversely, an inhibitor of BTK used clinically (ibrutinib) induces bioenergetic stress responses that in turn affect ibrutinib resistance. Although the detailed molecular mechanisms are still to be defined, our work shows for the first time that in primary B cells, metabolic stressors enhance BTK signaling and suggest that metabolic rewiring to hyperglycemia affects ibrutinib resistance in TP53 deficient chronic lymphocytic leukemia (CLL) lymphocytes.

SUBMITTER: Sharif-Askari B

PROVIDER: S-EPMC6667467 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Bruton's tyrosine kinase is at the crossroads of metabolic adaptation in primary malignant human lymphocytes.

Sharif-Askari Bahram B Doyon Daniel D Paliouras Miltiadis M Aloyz Raquel R

Scientific reports 20190730 1

In this work we explored metabolic aspects of human primary leukemic lymphocytes that hold a potential impact on the treatment of Bruton tyrosine kinase (BTK)-driven diseases. Our results suggest that there is crosstalk between Bruton tyrosine kinase (BTK) signaling and bioenergetic stress responses. In primary chronic lymphocytic leukemia (CLL) lymphocytes, pharmacological interference with mitochondrial ATP synthesis or glucose metabolism affects BTK activity. Conversely, an inhibitor of BTK u ...[more]

PMID: 31363127

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2015-10-24 | GSE41825 | GEO

Bruton's Tyrosine Kinase Regulates TLR9 but not TLR7 Signaling in Human pDCs

2015-10-24 | E-GEOD-41825 | biostudies-arrayexpress