Treatment-Emergent Resistance to Asciminib in Chronic Myeloid Leukemia Patients Due to Myristoyl-Binding Pocket-Mutant of BCR::ABL1/A337V Can Be Effectively Overcome with Dasatinib Treatment
Bibliographic record
Abstract
Despite the groundbreaking success of tyrosine kinase inhibitor therapy, the management of chronic myeloid leukemia patients is often impaired by resistance due to specific point mutations in the BCR::ABL1 oncogene. Upon classical ATP-competitive inhibitor treatment, these single nucleotide variants occur in the tyrosine kinase domain of ABL1. The novel allosteric BCR::ABL1 inhibitor asciminib was developed to treat CML patients alone or in combination to overcome or potentially prevent these treatment-emergent TKD mutations. Here, we present a case of a patient undergoing first-line asciminib therapy, and subsequently develop a specific BCR::ABL1/A337V point mutation, which resulted in asciminib resistance. Switching to second-line dasatinib treatment successfully overcame asciminib resistance and helped to achieve a deep molecular response. In case of treatment failures caused by single asciminib-specific point mutations, dasatinib therapy is a feasible choice.
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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) | 0.000 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".