X-Linked Clonality Analysis and Quantitative JAK2V617F Assessment Reveals a Strong Association between Clonality and JAK2V617F in PV but Not in ET/MMM, and Identifies a Subset of JAK2V617F Negative ET and MMM Patients with Clonal Hematopoiesis.
Bibliographic record
Abstract
Abstract Polycythemia vera (PV), essential thrombocythemia (ET), and myeloid metaplasia with myelofibrosis (MMM) are categorized as a set of phenotypically related myeloproliferative disorders (MPD). Recent work has identified a somatic mutation in the JAK2 tyrosine kinase (JAK2V617F) in the majority of PV and in a subset of ET and MMM. As most, but not all, patients with MPD have clonal granulocytes, we sought to determine if there was a relationship between granulocyte clonality and JAK2V617F mutational status using a quantitative clonality assay for the human androgen receptor gene (HUMARA) and a quantitative real-time PCR assay for JAK2V617F. 168 of 190 female MPD patients were informative for the HUMARA polymorphism, and 121 patients (72%) had allele skewing consistent with clonal granulopoiesis including 80% of MMM, 75% of PV, and 67% of ET. The quantitative real-time PCR assay for JAK2V617F detected the JAK2V617F allele in 98.8% of PV, 69% of ET, and 33% of MMM, and was more sensitive than direct sequencing. A significant correlation between the degree of allele skewing and quantitative JAK2V617F allelic ratio was observed in PV (p<0.0001) but not in ET (p= 0.2) or MMM (p=0.771). In addition, a subset of patients with ET and MMM with clonal granulocytes had JAK2V617F present in some, but not all, clonal granulocytes. These data suggest acquisition of the JAK2V617F mutation may be sufficient for the development of PV, but additional genetic events are necessary to cooperate with JAK2V617F in ET and MMM. Most importantly, we identified a subset of patients with ET (23%) and MMM (17%), but not PV, with clonal granulocytes who were JAK2V617F negative. A high-throughput screen for novel activating mutations in signal transduction pathways in JAK2V617F negative ET and MMM is warranted.
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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".