Clinico-Biological Features and Prognostic Significance of PML/RARα Isoforms in Adult Patients with Acute Promyelocytic Leukemia Treated with All Trans Retinoic Acid (ATRA) and Chemotherapy
Bibliographic record
Abstract
Debate exists over the clinical relevance of molecular heterogeneity of acute promyelocytic leukemia (APL). Based on the genomic breakpoint in PML gene, three different PML/RARalpha isoforms are recognized: intron 3 [short (S)], intron 6 [long (L)] and exon 6 [variable (V)]. Studies on the prognostic significance of PML/RARalpha isoforms have reported contradictory results. This discrepancy may be related to differences in the treatment protocols, as some studies used ATRA alone during induction therapy. We analyzed the clinical course of 61 consecutive newly diagnosed patients with a genetically confirmed diagnosis of APL, treated with ATRA and chemotherapy at Princess Margaret Hospital from January 1994 to January 2002. The results of RT PCR at diagnosis were available on 48 patients. In this study, we report on clinico-biological features and prognostic significance of PML/RARalpha isoforms in these 48 patients. Of 48 patients, 19(40%) had the S isoform and 29 (60%) had the L/V isoform. Median white blood cell (WBC) count for patients with S isoform was 8.6 [interquartile range Q1-Q3 i.e. IQR 3.2-29] compared to 1.8 [IQR 1.0-4.9] for the L/V isoform group (P 0.001). No difference was seen in number of patients achieving of molecular remission after induction and consolidation treatment in the two-isoform groups. The patients with S isoform had significantly inferior relapse-free survival (RFS) at 3 years compared to L/V isoform patients [48% (95% C.I. 19 77) vs. 92% (95% C.I. 82-100), P0.006]. In a univariate analysis, S isoform status (P 0.006) and high WBC count ( > or = 5 x 10(9)+/l) (P 0.017) were significant prognostic factors for RFS. No difference in overall survival was seen between the two isoform groups (P 0.35). Our results suggest that based on molecular characterization, it may be possible to identify a subgroup of APL patients at higher-risk of relapse.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| 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".