Decreased expression level of SH2 domain‐containing protein tyrosine phosphatase‐1 (Shp1) is associated with progression of chronic myeloid leukaemia
Bibliographic record
Abstract
Abstract Chronic myeloid leukaemia (CML) is characterized by t(9;22)(q34;q11) and the aberrant expression of the fusion protein Bcr‐Abl that leads to constitutive activation of c‐Abl kinase. Bcr‐Abl plays a major role in the development and progression of CML through chronic, accelerated, and blast phases. The interaction between Bcr‐Abl and other oncogenic molecules has been extensively documented. Nonetheless, negative regulatory mechanisms of Bcr‐Abl are not completely defined. One major inhibitory pathway is mediated via the SH2 domain‐containing protein tyrosine phosphatase Shp1. In the present study, we demonstrate that Shp1 levels are markedly decreased in advanced stage CML patients compared with those in chronic phase. This process was independent of DNA methylation. Furthermore, we did not detect mutations in the Shp1 gene in CML cell lines or patient samples. These data suggest that the decrease in Shp1 in advanced stage CML patients is due to post‐transcriptional modifications. Our findings suggest that the decrease in Shp1 expression levels plays a role in the progression of CML. Also, the decrease in Shp1 and subsequently its inhibitory effect on Bcr‐Abl could provide an explanation for imatinib resistance seen in advanced stage CML patients. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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".