Clinicopathologic and Prognostic Significance of Bruton’s Tyrosine Kinase Expression in Diffuse Large B-Cell Lymphoma

Background/Aim: Bruton's tyrosine kinase (BTK)-mediated B-cell-receptor signaling drives lymphomagenesis of diffuse large B-cell lymphoma (DLBCL). We investigated the clinicopathological significance of BTK positivity in DLBCL according to known molecules related to resistance to BTK inhibitors...

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Bibliographic Details
Published in:Anticancer research 2021-11, Vol.41 (11), p.5677-5692
Main Authors: HAN, YEON BI, YANG, JEONG MI, KWON, HYUN JUNG, LEE, JEONG-OK, LEE, JONG SEOK, PAIK, JIN HO
Format: Article
Language:English
Subjects:
Amplification
Apoptosis
B-cell lymphoma
Bruton's tyrosine kinase
Cyclophosphamide
Doxorubicin
Helix-loop-helix proteins (basic)
Kinases
Lymphocytes B
Lymphoma
Myc protein
Prednisone
Protein-tyrosine kinase
Rituximab
Subgroups
Translocation
Tyrosine
Vincristine
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Summary:Background/Aim: Bruton's tyrosine kinase (BTK)-mediated B-cell-receptor signaling drives lymphomagenesis of diffuse large B-cell lymphoma (DLBCL). We investigated the clinicopathological significance of BTK positivity in DLBCL according to known molecules related to resistance to BTK inhibitors [BCL2 apoptosis regulator (BCL2)/MYC proto-oncogene, bHLH transcription factor (MYC)]. Patients and Methods: We evaluated BTK expression immunohistochemically in 106 DLBCLs considering their BCL2/MYC status. Results: Considering the whole cohort, BTK was expressed in 65.1%, including 70.4% (50/71) of non-germinal center B-cell-like (non-GCB) subtype; BCL2 expression was detected in 60.4%, MYC expression in 15.1%, MYC translocation in 4.2% (4/96) and MYC gain/amplification in 7.6% (8/105). Overall and in the non-GCB cohort, BTK positively correlated with high international prognostic index (both p=0.005) and stage (p=0.006 and p=0.002), and with BCL2 intensity (p=0.005 and p=0.026, respectively); MYC gain/amplification total cohort (p=0.038). Moreover, high risk, defined as co-expression of BTK and either or both BCL2/MYC, independently predicted shorter progression-free survival in patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) (all R-CHOP-treated patients: hazard ratio=2.565, p=0.044; R-CHOP-treated non-GCB subgroup: HR=3.833, p=0.019). Conclusion: BTK expression may be utilized to stratify risk in patients with DLBCL.
ISSN:0250-7005
1791-7530
DOI:10.21873/anticanres.15384