Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type Diffuse Large B Cell Lymphoma

Findlay Bewicke-Copley; Koorosh Korfi; Shamza Araf; Brendan Hodkinson; Emil Kumar; Thomas Cummin; Margaret Ashton-Key; Sharon L Barrans; Suzan JL van Hoppe; Cathy Burton; Mohamed Elshiekh; Simon Rule; Nicola Crosbie; Andrew James Clear; Maria Calaminici; Hendrik Friedrich Peter Runge; Robert K Hills; David W. Scott; Lisa M Rimsza; Geetha Menon; Chulin Sha; John Davies; Ai Nagano; Andrew John Davies; Daniel Painter; Alexandra Smith; John G Gribben; Kikkeri N Naresh; David Robert Westhead; Jessica Okosun; Andrew J Steele; Daniel J Hodson; Sriram Balasubramanian; Peter W. M. Johnson; Jun Wang; Jude Fitzgibbon

doi:10.1182/bloodadvances.2022007536

Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type Diffuse Large B Cell Lymphoma

Findlay Bewicke-Copley, Koorosh Korfi, Shamza Araf, Brendan Hodkinson, Emil Kumar, Thomas Cummin, Margaret Ashton-Key, Sharon L Barrans, Suzan JL van Hoppe, Cathy Burton, Mohamed Elshiekh, Simon Rule, Nicola Crosbie, Andrew James Clear, Maria Calaminici, Hendrik Friedrich Peter Runge, Robert K Hills, David W. Scott, Lisa M Rimsza, Geetha MenonChulin Sha, John Davies, Ai Nagano, Andrew John Davies, Daniel Painter, Alexandra Smith, John G Gribben, Kikkeri N Naresh, David Robert Westhead, Jessica Okosun, Andrew J Steele, Daniel J Hodson, Sriram Balasubramanian, Peter W. M. Johnson, Jun Wang, Jude Fitzgibbon

Health Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

Despite the effectiveness of immuno-chemotherapy, 40\cell lymphoma (DLBCL) experience relapse or refractory disease. Longitudinal studies have previously focused on the mutational landscape of relapse but fell short of providing a consistent relapse-specific genetic signature. In our study, we have focussed attention on the changes in gene expression profile accompanying DLBCL relapse using archival paired diagnostic/relapse specimens from 38 de novo DLBCL patients. Cell of origin remained stable from diagnosis to relapse in 80\ with only a single patient showing COO switching from ABC to GCB. Analysis of the transcriptomic changes that occur following relapse suggest ABC and GCB relapses are mediated via different mechanisms. We developed a 30-gene discriminator for ABC-DLBCLs derived from relapse-associated genes, that defined clinically distinct high and low risk subgroups in ABC-DLBCLs at diagnosis in datasets comprising both population-based and clinical trial cohorts. This signature also identified a population of \lt;60-year-old patients with superior PFS and OS treated with Ibrutinib-R-CHOP as part of the PHOENIX trial. Altogether this new signature adds to the existing toolkit of putative genetic predictors now available in DLBCL that can be readily assessed as part of prospective clinical trials.

Original language	English
Journal	Blood Advances
DOIs	https://doi.org/10.1182/bloodadvances.2022007536
Publication status	Published - 10 Aug 2022

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10.1182/bloodadvances.2022007536

Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type Diffuse Large B Cell Lymphoma
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Cite this

Bewicke-Copley, F., Korfi, K., Araf, S., Hodkinson, B., Kumar, E., Cummin, T., Ashton-Key, M., Barrans, S. L., van Hoppe, S. JL., Burton, C., Elshiekh, M., Rule, S., Crosbie, N., Clear, A. J., Calaminici, M., Runge, H. F. P., Hills, R. K., Scott, D. W., Rimsza, L. M., ... Fitzgibbon, J. (2022). Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type Diffuse Large B Cell Lymphoma. Blood Advances. https://doi.org/10.1182/bloodadvances.2022007536

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title = "Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type Diffuse Large B Cell Lymphoma",

abstract = "Despite the effectiveness of immuno-chemotherapy, 40\cell lymphoma (DLBCL) experience relapse or refractory disease. Longitudinal studies have previously focused on the mutational landscape of relapse but fell short of providing a consistent relapse-specific genetic signature. In our study, we have focussed attention on the changes in gene expression profile accompanying DLBCL relapse using archival paired diagnostic/relapse specimens from 38 de novo DLBCL patients. Cell of origin remained stable from diagnosis to relapse in 80\ with only a single patient showing COO switching from ABC to GCB. Analysis of the transcriptomic changes that occur following relapse suggest ABC and GCB relapses are mediated via different mechanisms. We developed a 30-gene discriminator for ABC-DLBCLs derived from relapse-associated genes, that defined clinically distinct high and low risk subgroups in ABC-DLBCLs at diagnosis in datasets comprising both population-based and clinical trial cohorts. This signature also identified a population of \lt;60-year-old patients with superior PFS and OS treated with Ibrutinib-R-CHOP as part of the PHOENIX trial. Altogether this new signature adds to the existing toolkit of putative genetic predictors now available in DLBCL that can be readily assessed as part of prospective clinical trials.",

author = "Findlay Bewicke-Copley and Koorosh Korfi and Shamza Araf and Brendan Hodkinson and Emil Kumar and Thomas Cummin and Margaret Ashton-Key and Barrans, {Sharon L} and {van Hoppe}, {Suzan JL} and Cathy Burton and Mohamed Elshiekh and Simon Rule and Nicola Crosbie and Clear, {Andrew James} and Maria Calaminici and Runge, {Hendrik Friedrich Peter} and Hills, {Robert K} and Scott, {David W.} and Rimsza, {Lisa M} and Geetha Menon and Chulin Sha and John Davies and Ai Nagano and Davies, {Andrew John} and Daniel Painter and Alexandra Smith and Gribben, {John G} and Naresh, {Kikkeri N} and Westhead, {David Robert} and Jessica Okosun and Steele, {Andrew J} and Hodson, {Daniel J} and Sriram Balasubramanian and Johnson, {Peter W. M.} and Jun Wang and Jude Fitzgibbon",

note = "Uploaded in accordance with the publisher{\textquoteright}s self-archiving policy. Further copying may not be permitted; contact the publisher for details",

year = "2022",

month = aug,

day = "10",

doi = "10.1182/bloodadvances.2022007536",

language = "English",

journal = "Blood Advances",

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Bewicke-Copley, F, Korfi, K, Araf, S, Hodkinson, B, Kumar, E, Cummin, T, Ashton-Key, M, Barrans, SL, van Hoppe, SJL, Burton, C, Elshiekh, M, Rule, S, Crosbie, N, Clear, AJ, Calaminici, M, Runge, HFP, Hills, RK, Scott, DW, Rimsza, LM, Menon, G, Sha, C, Davies, J, Nagano, A, Davies, AJ, Painter, D , Smith, A, Gribben, JG, Naresh, KN, Westhead, DR, Okosun, J, Steele, AJ, Hodson, DJ, Balasubramanian, S, Johnson, PWM, Wang, J & Fitzgibbon, J 2022, 'Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type Diffuse Large B Cell Lymphoma', Blood Advances. https://doi.org/10.1182/bloodadvances.2022007536

TY - JOUR

T1 - Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type Diffuse Large B Cell Lymphoma

AU - Bewicke-Copley, Findlay

AU - Korfi, Koorosh

AU - Araf, Shamza

AU - Hodkinson, Brendan

AU - Kumar, Emil

AU - Cummin, Thomas

AU - Ashton-Key, Margaret

AU - Barrans, Sharon L

AU - van Hoppe, Suzan JL

AU - Burton, Cathy

AU - Elshiekh, Mohamed

AU - Rule, Simon

AU - Crosbie, Nicola

AU - Clear, Andrew James

AU - Calaminici, Maria

AU - Runge, Hendrik Friedrich Peter

AU - Hills, Robert K

AU - Scott, David W.

AU - Rimsza, Lisa M

AU - Menon, Geetha

AU - Sha, Chulin

AU - Davies, John

AU - Nagano, Ai

AU - Davies, Andrew John

AU - Painter, Daniel

AU - Smith, Alexandra

AU - Gribben, John G

AU - Naresh, Kikkeri N

AU - Westhead, David Robert

AU - Okosun, Jessica

AU - Steele, Andrew J

AU - Hodson, Daniel J

AU - Balasubramanian, Sriram

AU - Johnson, Peter W. M.

AU - Wang, Jun

AU - Fitzgibbon, Jude

N1 - Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details

PY - 2022/8/10

Y1 - 2022/8/10

N2 - Despite the effectiveness of immuno-chemotherapy, 40\cell lymphoma (DLBCL) experience relapse or refractory disease. Longitudinal studies have previously focused on the mutational landscape of relapse but fell short of providing a consistent relapse-specific genetic signature. In our study, we have focussed attention on the changes in gene expression profile accompanying DLBCL relapse using archival paired diagnostic/relapse specimens from 38 de novo DLBCL patients. Cell of origin remained stable from diagnosis to relapse in 80\ with only a single patient showing COO switching from ABC to GCB. Analysis of the transcriptomic changes that occur following relapse suggest ABC and GCB relapses are mediated via different mechanisms. We developed a 30-gene discriminator for ABC-DLBCLs derived from relapse-associated genes, that defined clinically distinct high and low risk subgroups in ABC-DLBCLs at diagnosis in datasets comprising both population-based and clinical trial cohorts. This signature also identified a population of \lt;60-year-old patients with superior PFS and OS treated with Ibrutinib-R-CHOP as part of the PHOENIX trial. Altogether this new signature adds to the existing toolkit of putative genetic predictors now available in DLBCL that can be readily assessed as part of prospective clinical trials.

AB - Despite the effectiveness of immuno-chemotherapy, 40\cell lymphoma (DLBCL) experience relapse or refractory disease. Longitudinal studies have previously focused on the mutational landscape of relapse but fell short of providing a consistent relapse-specific genetic signature. In our study, we have focussed attention on the changes in gene expression profile accompanying DLBCL relapse using archival paired diagnostic/relapse specimens from 38 de novo DLBCL patients. Cell of origin remained stable from diagnosis to relapse in 80\ with only a single patient showing COO switching from ABC to GCB. Analysis of the transcriptomic changes that occur following relapse suggest ABC and GCB relapses are mediated via different mechanisms. We developed a 30-gene discriminator for ABC-DLBCLs derived from relapse-associated genes, that defined clinically distinct high and low risk subgroups in ABC-DLBCLs at diagnosis in datasets comprising both population-based and clinical trial cohorts. This signature also identified a population of \lt;60-year-old patients with superior PFS and OS treated with Ibrutinib-R-CHOP as part of the PHOENIX trial. Altogether this new signature adds to the existing toolkit of putative genetic predictors now available in DLBCL that can be readily assessed as part of prospective clinical trials.

U2 - 10.1182/bloodadvances.2022007536

DO - 10.1182/bloodadvances.2022007536

M3 - Article

SN - 2473-9529

JO - Blood Advances

JF - Blood Advances

ER -