Diffuse large B-cell lymphoma in Southeast Asian cohort

Expression patterns of B-cell receptor (BCR) repertoire and its linkage with molecular subtypes and response to R-CHOP therapy

Noraidah Masir, Ariz Akhter, Tariq M. Roshan, Chandramaya Sabrina Florence, Faridah Abdul-Rahman, Nor Rafeah Tumian, Phang Kean-Chang, Ghaleb Elyamany, Meer Taher Shabani-Rad, Adnan Mansoor

Research output: Contribution to journalArticle

Abstract

Aims: Heightened B-cell receptor (BCR) activity in diffuse large B-cell lymphoma (DLBCL) is well established, and a subset of patients with relapsed DLBCL can benefit from BCR-targeted therapies. Universal outreach of such emerging therapies mandates forming a global landscape of BCR molecular signalling in DLBCL, including Southeast Asia. Methods: 79 patients with DLBCL (nodal, 59% and extranodal, 41%) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS). Results: Activated B-cell (ABC) type DLBCL constituted 49% (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37%) and revealed poor prognosis (p=0.013). In ABC-DLBCL, high BTK expression exerted poor response to R-CHOP, while OS in ABC-DLBCL with low BTK expression was similar to GCB-DLBCL subtype (p=0.004). High LYN expression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression of BTK/LYN (BTKhigh/LYNhigh) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, high BTK and LYN expression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05). Conclusions: Our data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.

Original languageEnglish
JournalJournal of Clinical Pathology
DOIs
Publication statusPublished - 1 Jan 2019

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Lymphoma, Large B-Cell, Diffuse
B-Lymphocytes
Germinal Center
Therapeutics
Southeastern Asia
Survival
NF-kappa B
Vincristine
Prednisone
Doxorubicin
Cyclophosphamide
Up-Regulation
Multivariate Analysis

Keywords

  • cell biology
  • genetics
  • lymphoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Diffuse large B-cell lymphoma in Southeast Asian cohort : Expression patterns of B-cell receptor (BCR) repertoire and its linkage with molecular subtypes and response to R-CHOP therapy. / Masir, Noraidah; Akhter, Ariz; Roshan, Tariq M.; Florence, Chandramaya Sabrina; Abdul-Rahman, Faridah; Tumian, Nor Rafeah; Kean-Chang, Phang; Elyamany, Ghaleb; Shabani-Rad, Meer Taher; Mansoor, Adnan.

In: Journal of Clinical Pathology, 01.01.2019.

Research output: Contribution to journalArticle

Masir, Noraidah ; Akhter, Ariz ; Roshan, Tariq M. ; Florence, Chandramaya Sabrina ; Abdul-Rahman, Faridah ; Tumian, Nor Rafeah ; Kean-Chang, Phang ; Elyamany, Ghaleb ; Shabani-Rad, Meer Taher ; Mansoor, Adnan. / Diffuse large B-cell lymphoma in Southeast Asian cohort : Expression patterns of B-cell receptor (BCR) repertoire and its linkage with molecular subtypes and response to R-CHOP therapy. In: Journal of Clinical Pathology. 2019.
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abstract = "Aims: Heightened B-cell receptor (BCR) activity in diffuse large B-cell lymphoma (DLBCL) is well established, and a subset of patients with relapsed DLBCL can benefit from BCR-targeted therapies. Universal outreach of such emerging therapies mandates forming a global landscape of BCR molecular signalling in DLBCL, including Southeast Asia. Methods: 79 patients with DLBCL (nodal, 59{\%} and extranodal, 41{\%}) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS). Results: Activated B-cell (ABC) type DLBCL constituted 49{\%} (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37{\%}) and revealed poor prognosis (p=0.013). In ABC-DLBCL, high BTK expression exerted poor response to R-CHOP, while OS in ABC-DLBCL with low BTK expression was similar to GCB-DLBCL subtype (p=0.004). High LYN expression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression of BTK/LYN (BTKhigh/LYNhigh) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, high BTK and LYN expression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05). Conclusions: Our data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.",
keywords = "cell biology, genetics, lymphoma",
author = "Noraidah Masir and Ariz Akhter and Roshan, {Tariq M.} and Florence, {Chandramaya Sabrina} and Faridah Abdul-Rahman and Tumian, {Nor Rafeah} and Phang Kean-Chang and Ghaleb Elyamany and Shabani-Rad, {Meer Taher} and Adnan Mansoor",
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T1 - Diffuse large B-cell lymphoma in Southeast Asian cohort

T2 - Expression patterns of B-cell receptor (BCR) repertoire and its linkage with molecular subtypes and response to R-CHOP therapy

AU - Masir, Noraidah

AU - Akhter, Ariz

AU - Roshan, Tariq M.

AU - Florence, Chandramaya Sabrina

AU - Abdul-Rahman, Faridah

AU - Tumian, Nor Rafeah

AU - Kean-Chang, Phang

AU - Elyamany, Ghaleb

AU - Shabani-Rad, Meer Taher

AU - Mansoor, Adnan

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Aims: Heightened B-cell receptor (BCR) activity in diffuse large B-cell lymphoma (DLBCL) is well established, and a subset of patients with relapsed DLBCL can benefit from BCR-targeted therapies. Universal outreach of such emerging therapies mandates forming a global landscape of BCR molecular signalling in DLBCL, including Southeast Asia. Methods: 79 patients with DLBCL (nodal, 59% and extranodal, 41%) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS). Results: Activated B-cell (ABC) type DLBCL constituted 49% (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37%) and revealed poor prognosis (p=0.013). In ABC-DLBCL, high BTK expression exerted poor response to R-CHOP, while OS in ABC-DLBCL with low BTK expression was similar to GCB-DLBCL subtype (p=0.004). High LYN expression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression of BTK/LYN (BTKhigh/LYNhigh) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, high BTK and LYN expression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05). Conclusions: Our data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.

AB - Aims: Heightened B-cell receptor (BCR) activity in diffuse large B-cell lymphoma (DLBCL) is well established, and a subset of patients with relapsed DLBCL can benefit from BCR-targeted therapies. Universal outreach of such emerging therapies mandates forming a global landscape of BCR molecular signalling in DLBCL, including Southeast Asia. Methods: 79 patients with DLBCL (nodal, 59% and extranodal, 41%) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS). Results: Activated B-cell (ABC) type DLBCL constituted 49% (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37%) and revealed poor prognosis (p=0.013). In ABC-DLBCL, high BTK expression exerted poor response to R-CHOP, while OS in ABC-DLBCL with low BTK expression was similar to GCB-DLBCL subtype (p=0.004). High LYN expression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression of BTK/LYN (BTKhigh/LYNhigh) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, high BTK and LYN expression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05). Conclusions: Our data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.

KW - cell biology

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KW - lymphoma

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