Natural Killer (NK) or NK/T Cell Lineage Large Granular Lymphocytosis Associated with Dasatinib Therapy for Philadelphia Chromosome Positive Leukemia.
Bibliographic record
Abstract
Abstract Dasatinib, a dual tyrosine kinase inhibitor, is known to modulate or suppress T-cell activation and proliferation. We report a series of patients of chronic peripheral lymphocytosis development, identified as natural killer (NK) cells or NK/T-cells based on their large granular lymphocyte (LGL) morphologies and CD16+CD56+CD3− or CD3+ immunophenotypic profiles during dasatinib therapy. All cases that developed LGL lymphocytosis achieved optimal molecular response (8/8 in LGL+ patients vs 3/10 in LGL− patients, p=0.002). A 51Cr release assay demonstrated that NK cell cytotoxicity has been enhanced in a case of LGL lymphocytosis compared to normal healthy donors (Figure 1), and that NK cell cytotoxicity in dasatinib-responders was superior to that in non-responders (Figure 2). In summary, the present study suggests that NK or NK/T cell lineage LGL lymphocytosis develops associated with dasatinib therapy and that LGL might have a therapeutic effect on Ph+ leukemic cells. Figure 1. Cytotoxicity of NK cells isolated from the patients developing large granular lymphocytosis following dasatinib therapy as assessed by 51Cr release assays using target cells as K562 (A) and T2 cell line (B) as target cells. Figure 1. Cytotoxicity of NK cells isolated from the patients developing large granular lymphocytosis following dasatinib therapy as assessed by 51Cr release assays using target cells as K562 (A) and T2 cell line (B) as target cells. Figure 2. The result of 51Cr release assays comparing cytotoxicity of NK cells isolated from patients responding to dasatinib therapy (responder) and not responding (non-responder) following dasatinib therapy using K562 cell line as target cells. Figure 2. The result of 51Cr release assays comparing cytotoxicity of NK cells isolated from patients responding to dasatinib therapy (responder) and not responding (non-responder) following dasatinib therapy using K562 cell line as target cells.
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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 | 0.000 | 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) | 0.001 | 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".