Clinical Significance of bZIP In-Frame CEBPA-Mutated Normal Karyotype Acute Myeloid Leukemia
Bibliographic record
Abstract
Purpose We evaluated the characteristics of CCAAT/enhancer-binding protein α (<i>CEBPA</i>) mutations and the significance of a basic leucine zipper in-frame mutation (bZIP<sup>in-f</sup>) of <i>CEBPA</i> in patients with acute myeloid leukemia with a normal karyotype.Materials and Methods Based on updated knowledge of <i>CEBPA</i> mutations, we conducted next-generation sequencing analyses in a previously established real-world cohort.Results Among 78 of a total of 395 patients (19.7%), 50 had bZIP<sup>in-f</sup> <i>CEBPA</i>, and 28 had non-bZIP<sup>in-f</sup> <i>CEBPA</i>. In the multivariate analysis, patients with <i>NPM1</i><sup>mut</sup>, those with bZIP<sup>in-f</sup> <i>CEBPA</i>, and those who underwent allogeneic hematopoietic cell transplantation (allo-HCT) had favorable overall survival (OS), but <i>FLT3</i>-ITD<sup>mut</sup> was a poor prognostic indicator. For relapse-free survival (RFS) and cumulative incidence of relapse, bZIP<sup>in-f</sup> <i>CEBPA</i>, and allo-HCT were associated with favorable outcomes; <i>FLT3</i>-ITD<sup>pos</sup> was associated with worse outcomes. In the <i>CEBPA</i> double-mutated group (<i>CEBPA</i><sup>dm</sup>), bZIP<sup>in-f</sup> <i>CEBPA</i> was associated with superior outcomes in terms of OS (p=0.007) and RFS (p=0.007) compared with non-bZIP<sup>in-f</sup> <i>CEBPA</i>. Of 50 patients with bZIP<sup>in-f</sup> <i>CEBPA</i>, 36 patients had at least one mutation. When grouped by the presence of mutations in chromatic/DNA modifiers (C), cohesion complex (C), and splicing genes (S) (CCS mutations), CCS-mutated bZIP<sup>in-f</sup> <i>CEBPA</i> was associated with poor OS (p=0.044; hazard ratio [HR], 2.419) and a trend in inferior RFS (p=0.186; HR, 1.838).Conclusion Only bZIP<sup>in-f</sup> <i>CEBPA</i> was associated with favorable outcomes in patients with <i>CEBPA</i><sup>dm</sup>. However, some mutations accompanying bZIP<sup>in-f</sup> <i>CEBPA</i> showed inferior OS; thus, further studies with larger numbers of patients are required for clear conclusions of the significance of bZIP<sup>in-f</sup> <i>CEBPA<i>.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| 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".