TALE Homeoproteins as HOX11-Interacting Partners in T-cell Leukemia
Bibliographic record
Abstract
The mammalian PBX and Meis proteins belong to the TALE (three-amino acid-loop-extension) superfamily of homeodomain-containing transcription factors. Members of both the PBX and Meis groups have been implicated in tumorigenesis and are known to cooperatively bind DNA with Class I (clustered) HOX homeoproteins. Here we show that PBX and Meis homeoproteins cooperatively bind the PBX-responsive sequence in vitro with the oncoprotein encoded by the non-clustered homeobox gene HOX11 activated by the t(10;14)(q24;q11) chromosomal translocation in T-cell acute lymphoblastic leukemia (T-ALL). An FPWME motif N-terminal to the homeodomain is required for interaction with PBX proteins, which appears to confer DNA-binding specificity to HOX11. PBX proteins are highly expressed in HOX11 immortalized/transformed hematopoietic cells; in particular, the 10q24 translocation-carrying T-ALL Sil and K3P lines were found to selectively express PBX2. Ectopic retroviral-directed overexpression of PBX2 in concert with HOX11 in NIH3T3 cells resulted in decreased contact inhibition of growth as evidenced by focus formation in confluent cell monolayers. The accumulated data are thus consistent with a role of TALE homeoproteins in HOX11-mediated leukemogenesis.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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; both teacher heads agree on what is shown here.
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".