Establishment of a t(11;19), KMT2A Rearranged B-ALL Cell Line for Preclinical Evaluation and Novel Therapeutics Development for Refractory Infant Leukemia
Bibliographic record
Abstract
Leukemia, diagnosed in children less than 12 months of age, is a rare condition with an aggressive disease presentation and poor response to conventional chemotherapeutic agents. In addition, the unique vulnerability of the affected population does not always permit the use of markedly intense regimens with higher doses of cytotoxic agents. However, the unique biology of these leukemic cells also provides opportunities for the identification of effective and potentially well-tolerated targeted therapeutic strategies. In this report, we describe the establishment and characterization of a cell line from the blasts of an infant diagnosed with refractory B-cell acute lymphoblastic leukemia (ALL) carrying the characteristic histone lysine methyltransferase 2A (KMT2A) gene rearrangement. This cell line consists of rapidly proliferating clones of cells with chemosensitivity patterns previously described for KMT2A rearranged leukemia cells, including relative resistance to glucocorticoids and sensitivity to cytarabine. We also show effective targetability with menin inhibitors, indicating the activity of abnormal KMT2A-related pathways and the potential utility of this cell line in comprehensive drug library screens. Overall, our findings report the establishment and in vitro validation of a cell line for research into key aspects of infant leukemia biology and targeted therapeutics development.
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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 | 0.001 | 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 | 0.001 |
| 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".