Follicular Lymphoma-associated BTK Mutations are Inactivating Resulting in Augmented AKT Activation.

ABSTRACT:

Purpose

On the basis of the recent discovery of mutations in Bruton tyrosine kinase (BTK) in follicular lymphoma, we studied their functional properties.

Experimental design

We identified novel somatic BTK mutations in 7% of a combined total of 139 follicular lymphoma and 11 transformed follicular lymphoma cases, none of which had received prior treatment with B-cell receptor (BCR) targeted drugs. We reconstituted wild-type (WT) and mutant BTK into various engineered lymphoma cell lines. We measured BCR-induced signal transduction events in engineered cell lines and primary human follicular lymphoma B cells.

Results

We uncovered that all BTK mutants destabilized the BTK protein and some created BTK kinase-dead mutants. The phospholipase C gamma 2 (PLCγ2)

SUBMITTER: Hu N 

PROVIDER: S-EPMC8046715 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature