Biological and clinical relevance of CD79 protein and gene expression in diffuse large B‐cell lymphoma
Bibliographic record
Abstract
Introduction: CD79B is a target of polatuzumab vedotin, an antibody–drug conjugate, which may improve the prognosis of both previously untreated and relapsed/refractory patients with diffuse large B-cell lymphoma (DLBCL). However, the biological and clinical significance of CD79B protein and gene expression in DLBCL is largely unknown. Methods: We retrospectively analyzed de novo DLBCL patients, who were diagnosed and received rituximab-based immunochemotherapy from 2008 through 2018 in the Okayama Hematology Study Group from Japan. Immunohistochemistry (IHC) staining was performed using a CD79B antibody (AT107-2), and protein expression was assessed based on H-score according to a previous study (Sehn L et al. JCO 2020). We also performed gene expression profile-based cell-of-origin (COO) classification, including double-hit signature (DHITsig) which has been renamed to dark zone signature (DZsig) (Waleed A et al. Blood 2022), using the NanoString DLBCL90 assay. Results: CD79B IHC expression was evaluable in 602 cases. We idefined two groups according to median H-score of CD79B expression: CD79Bhigh and CD79Blow. The COO subtypes were assigned as follows: 308 patients (51%) with activated B-cell-like (ABC)-DLBCL, 196 (33%) with germinal center B-cell-like (GCB)-DLBCL, 32 (5%) with DZsig-pos DLBCL and 66 (11%) with unclassified (UNC). H-score of CD79B was the lowest in patients with ABC-DLBCL followed by GCB-DLBCL and DZsig-pos DLBCL in ascending order (Kruskal–Wallis test P < .00001; Figure A). Indeed, CD79Blow tumors were significantly enriched in ABC-DLBCL (57%) compared to GCB-DLBCL (40%) and DZsig-pos DLBCL (22%), respectively (both, P < .001). Consistently, using publicly available DLBCL datasets (Schmitz et al. NEJM 2018 and Ennishi et al. JCO 2019), we revealed that CD79B gene expression was the lowest in ABC-DLBCL compared to GCB- and DHITsig-DLBCL (Kruskal–Wallis test P = .01; Figure B and C). The association of CD79B expression with COO prompted us to evaluate CD79B expression in normal germinal center B cells. Notably single-cell transcriptomic analyses of six reactive lymphoid tissues from publicly available datasets revealed that the lowest expression of CD79B was found in plasmablasts followed by light zone B cells and dark zone B cells in ascending order (Kruskal–Wallis test P < .0001), supporting the differential expression of CD79Baccording to COO subtype. CD79Blow group had significantly shorter overall survival (OS) in the total DLBCL cohort (log-rank, P < .001) and within ABC-DLBCL (P = .001, Figure D and E). Moreover, CD79B protein expression was significantly associated with OS after adjusting for International Prognostic Index in the total cohort (Cox regression model; P< .001). Keywords: Aggressive B-cell non-Hodgkin lymphoma, Diagnostic and Prognostic Biomarkers Conflicts of interests pertinent to the abstract. K. Sunami Honoraria: Celgene, Sanofi, BMS, Ono, Janssen Research funding: Takeda, AbbVie, GSK, Chugai, Otsuka, MSD, Novartis, Astellas Amgen, Pfizer, Parexel, Kyowa Kirin, Symbio, Agios Y. Hiramatsu Honoraria: Chugai Pharmaceutical Co, Nippon Shinyaku Co, Bristol Myers Squibb, Sanofi K.K. I. Yoshida Honoraria: Kyowa Kirin, Chugai, Eisai, Jannsen, Nippon-shinyaku, Otsuka, Symbio, Takeda, Sumitomo Pharma, Meiji Research funding: Kyowa Kirin, Chugai Y. Maeda Research funding: Chugai, Nippon-shinyaku Other remuneration: Chugai, Eisai, Otsuka, Kyowa Kirin, Takeda D. W. Scott Consultant or advisory role: Abbvie, AstraZeneca, Janssen, Incyte Honoraria: AstraZeneca Research funding: Janssen, Roche/Genentech D. Ennishi Honoraria: Chugai, Eisai, Kyowa Kirin Research funding: Nipponshinyaku, Chugai
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".