BCL11AXL Protein: Its Distribution in Normal and Malignant Tissues and Use as a Marker for Plasmacytoid Dendritic Cells.
Bibliographic record
Abstract
Abstract The B-cell lymphoma/leukaemia 11A (BCL11A) gene was first identified in the rare t(2;14)(p16;q32.3) translocation involving the IGH locus in aggressive B-cell chronic lymphocytic leukaemia (CLL) and, together with REL, is a candidate for the 2p16 chromosomal amplifications in B-cell malignancies. BCL11A encodes a Kruppel zinc finger transcription factor essential for pre-B-cell development and thymocyte maturation. Alternative RNA splicing generates at least three BCL11A transcripts encoding proteins that share a common N-terminus with the BCL11AXL transcript being the most abundant BCL11A transcript in normal tissues. We have produced a murine monoclonal antibody (BCL11A/123, isotype IgG1) specific for the BCL11AXL protein and, using this reagent, provide the first description of BCL11AXL protein distribution in normal and malignant human tissues. Initial studies using another antibody to the common N-terminus indicated the BCL11AXL protein to be the dominant isoform. In lymph node, tonsil and spleen, BCL11AXL expression was detected in B-cell nuclei in the mantle zone, germinal centers, interfollicular areas, splenic marginal zones and in tonsillar epithelium, but not in plasma cells or T cells. The differential expression of BCL11AXL in B-cell populations suggests its downregulation might be a requirement for plasma cell differentiation and is consistent with reports that BCL11A is transcriptionally repressed by Blimp-1. A subpopulation of cells, mostly B-cells, in the thymic medulla and scattered cells in the cortex were BCL11AXL+. Labeling of a very small number of CD3+ T-cells in the cortex and epithelial cells around the cortical periphery was also observed. Labeling of B-cell follicles in rat spleen demonstrated the BCL11A/123 epitope to be conserved across species. Another important finding was the high level expression of BCL11AXL in CD74+CD68+CD123+ plasmacytoid dendritic cells (pDCs). Publicly available microarray expression data are consistent with these findings, showing BCL11A transcripts to be present at high levels in peripheral blood B cells, in tonsil, lymph node and fetal brain with the highest expression in pDCs. BCL11AXL therefore represents an additional marker for the identification of pDCs and may be important in the differentiation and/or functional activity of this cell type. BCL11AXL was commonly detected in B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia and a subgroup of Hodgkin’s lymphomas, with the exception of multiple myeloma. Tumor cells in a small number of T-cell lymphomas (3/29) also expressed BCL11AXL. In a tissue microarray, comprising 107 cases of de novo DLBCL at diagnosis, BCL11AXL expression correlated with that of its interaction partner BCL6 and showed a trend towards increased overall survival. The study of this molecule should provide additional invaluable information concerning the possible role of BCL11A in lymphomagenesis.
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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 | 0.001 |
| 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) | 0.001 | 0.001 |
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".