The cytoplasmic truncated receptor tyrosine kinase ALK‐ homodimer immortalizes and cooperates with ras in cellular transformation
Bibliographic record
Abstract
ABSTRACT Anaplastic large‐cell lymphomas are highly associated with a chromosomal translocation t(2;5). This condition results in a chimeric protein NPM/ALK (nucleophosmin/anaplastic lymphoma kinase), in which the shuttle protein NPM is fused to the catalytic domain of the tyrosine receptor kinase ALK. Because the oncogenic potential of NPM/ALK is not well understood, we analyzed the effects of NPM/ALK and the specific contribution of ALK in a standardized cell culture system by using primary rat embryo cells (REC) as cellular targets. We demonstrate by several biological parameters that NPM/ALK is an immortalizing oncogene that provides unlimited, yet normal, growth potential to REC and, with cooperation with a c‐H‐ras oncogene, induces cellular transformation. Targeting NPM/ALK to the nucleus diminishes its oncogenicity, which indicates that the fusion protein exerts its action mainly in the cytoplasm. Expression of the mere catalytic domain of ALK is insufficient with regard to immortalization and transformation. However, reestablishing the potential of ALK to homodimerize by fusing the bacterial dimerization domain of the tetracycline repressor to ALK reenforces the immortalizing function. Collaboration of dimeric ALK with c‐H‐ras converted primary REC into aggressively growing tumor cell lines. These studies identify ALK as a new member of immortalizing oncoproteins that exerts its function within the cytoplasm.
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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) | 0.000 | 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) | 0.000 | 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 teacher head, 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".