Initially disadvantaged, TEL-AML1 cells expand and initiate leukemia in response to irradiation and cooperating mutations
Bibliographic record
Abstract
Although TEL-AML1 is present in one-fourth of childhood precursor B-cell acute lymphoblastic leukemia (pre-B ALL), the expression of the ETV6-RUNX1 gene encoding this fusion protein has been a poor initiator of leukemia in multiple mouse models. 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 To gain insight into why this common lesion does not readily initiate disease, we took advantage of a novel mouse model, in which TEL-AML1 expression was linked to a fluorescence marker and could be induced in a subset of hematopoietic cells during embryonic development. The laboratory of Corrinne Lobe had generated a reporter mouse in which enhanced green fluorescent protein (EGFP) was expressed following Cre-mediated excision (designated herein as ZEG mice), and subsequently generated an analogous mouse, in which a human TEL-AML1 encoding complementary DNA and an internal ribosomal entry site were placed upstream of EGFP (designated herein as TA1 mice). We crossed the inducible ZEG and TA1 mice with mice expressing Cre under the control of the Tie2(Tek) promoter, which is expressed in endothelial cells as well as during early hematopoietic development. These crosses resulted in mice carrying either the Tie2-Cre and inducible ZEG transgenes (Cre/ZEG mice) or the Tie2-Cre and inducible TA1 transgenes (Cre/TA1 mice). Mice carrying the inducible TA1 transgene but lacking Cre were also generated (Cre-/TA1+ control mice).
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
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".