Pharmacotherapeutic Options for Philadelphia Chromosome-Positive CML
Bibliographic record
Abstract
Chronic myeloid leukemia (CML) is a myeloproliferative disorder of hematopoietic stem cells. Identifying the leading mutation in BCR-ABL that causes CML made it possible to develop a targeted approach against this vastly disseminating disease. The active tyrosine kinase protein of BCR-ABL was effectively blocked with an identified tyrosine kinase inhibitor (TKI), imatinib. Imatinib became the first targeted therapy licensed for patients with chronic-phase CML and its introduction was associated with substantial improvements in response and survival compared with previous therapies. However, drug resistance towards imatinib therapy soon emerged and hence limited the complete eradication of CML in patients receiving imatinib. This is primarily due to the mutations within the ABL kinase domain, and to a lesser degree, due to residual disease after treatment. Nilotinib and dasatinib were soon introduced and showed improved clinical outcomes in patients intolerant and resistant to imatinib treatment. However, the T315I mutant overcame these agents along with imatinib, rendering the treatment ineffective. Exploring the kinase domain of the BCR-ABL protein and identifying key components involved in the signal transduction pathways is crucial towards understanding the disease and developing better strategic approaches towards combating it. In this review, we broadly discuss the current treatment options available against Philadelphia chromosome (Ph) positive BCR-ABL CML.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".