Molecular Screening for E255K and F359V Mutations in Non-Responders Iraqi Chronic Myeloid Leukemia Patients to Imatinib Mesylate Therapy
Bibliographic record
Abstract
Mutations in the kinase domain (KD) of BCR-ABL are the most prevalent mechanism of acquired resistance to first generation of tyrosine kinase inhibitor Imatinib Mesylate (IM) in chronic myeloid leukemia (CML) patients. Dasatinib and Nilotinib, the second generation of tyrosine kinase inhibitors (SGTKI), have been approved for second-line treatment of CML patients who demonstrate resistance to IM. The identification of E255K and F359Vmutations, which are considered highly resistant to SGTKI nilotinib, lead to a clear-cut decision in the choice of the appropriate SGTKI dasatinib. The aim of this study is to assess the frequency of mutations E255K and F359V in Iraqi CML patients who showed criteria of failure or suboptimal response to IM by using Allele Specific Oligonucleotid-Polymerase Chain Reaction (ASO-PCR). In this cross-section study, 70 patients were diagnosed clinically and hematologically as CML, who attended the Baghdad Medical City /Teaching Hospital/Hematology Unite, during the period between September 2011 to June 2012. They were on IM in different doses (400-800 mg/day) for at least one and a half year. Those patients were classified according to their responsiveness to IM into four groups according to European Leukemia Net. Also, 10 healthy age match subjects were included who served as technical negative control. Peripheral blood (PB) samples were taken from each subject. DNA was extracted using commercial available DNA extraction kit. Molecular screening for the presence of E255K and F359V mutations were done using ASO-PCR. The mean value of age of CML patients was 40.5 ± 2.56 years. Male to female ratio of CML patients was 1.12:1. The result of molecular screening for two mutations showed that all seventy CML patients were negative for both mutations. We conclude that the presence of other variants of studied mutations, another types of point mutations or other mechanisms for resistance to IM such as over expression of BCR-ABL, drug influx and efflux could be the causes of IM resistance.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 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".