Identification of TRA-1-60-Positive Cells As a Potent Refractory Population in Follicular Lymphomas
Bibliographic record
Abstract
Abstract Despite receiving Rituximab-combined chemotherapy, approximately half of follicular lymphoma (FL) patients suffer tumor recurrence, a major clinical issue. Retrieval of lymphoma stem-like cells from these poorly understood, intractable lymphomas would thus greatly ameliorate the cancer therapeutics. Here we demonstrate that the TRA-1-60-expressing cells are a unique population in FLs, converge to the conventional stem cell marker Oct3/4 and ALDH1-positive population, and strongly resist current agents against B-cell lymphomas. TRA-1-60 expression was detected in minor populations of resting B-lymphocytes inside germinal centers in reactive lymphoid tissue, whereas scattered TRA-1-60-expressing cells were detected in the marginal area of neoplastic follicles of FLs, close to small blood vessels. Translocation t(14;18) was thus detected in DNAs from the TRA-positive cells in all five patients' samples, which evinced the identical pattern of gene fusion as that of TRA-negative cells in the same tissue in 4 of 5 fresh frozen FL samples. Retrospective histological comparison between the recurrent and cognate primary tissues revealed that the number of TRA-1-60-positive lymphoma cells from R-CHOP treated FL subjects had increased four-fold relative to primary tissue, a finding corroborated by in vitro assay on Rituximab treated 2 cell lines, wherein TRA-positive cell numbers increased over ten to thirty-fold compared to the untreated sample. Moreover, TRA-1-60-positive cell population was markedly resistant to current therapeutic agents for B-cell lymphomas. Concordantly, small numbers of TRA-1-60-positive cells implanted subcutaneously into NOD/SCID mice evinced potent tumor-initiating capacity in vivo, where tumors were twelve-fold larger in volume (p=0.0021<0.005) and thirteen-fold heavier in weight (p=0.0015<0.005) compared to those xenografted from the TRA-negative cells. In conclusion, while further investigation for molecular insights will be necessary, it is now clear that TRA-1-60 should be a prominent focus among cellular markers in follicular lymphoma research, by which we ultimately hope to explain clinical intractability against combination-Rituximab and other therapies, and to better understand the stemness among a range of lymphoma cell types. Disclosures Maeda: Mundipharma KK: Research Funding.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".