Possible Selection for the Jak2 V617F Mutation in Bone Marrow Failure
Bibliographic record
Abstract
Abstract The acquired JAK2 V617F mutation has been well documented to be common in the classical myeloproliferative disorders. As it is an activating mutation in a kinase involved in proliferative signaling in hematopoietic cells, it is presumed to play an etiopathogenic role. The same acquired JAK2 V617F mutation has been described in other hematological disorders such as myelodysplastic syndrome with a prevalence which, though much lower than in myeloproliferative disorders, exceeds what could be attributed to the chance coincidence of two rare disorders. The direction of causality in this association is unclear. CASE DESCRIPTION: A 42 year old woman initially presented at the age of six with anemia and was subsequently diagnosed with congenital dyserythropoietic anemia (CDA) type I. At initial presentation her other blood counts, including platelets, were normal. When she returned to hematology clinic as an adult, her anemia persisted, but she had elevated platelet and white blood counts. Bone marrow biopsy showed hypercellularity with increased representation of the myeloid and megakaryocyte lineages. It also showed megaloblastoid dyserythropoiesis and binucleate erythroid precursors. These changes are consistent with essential thrombocythemia superimposed on CDA type I. The marrow cells were heterozygous for the JAK2 V617F mutation. DISCUSSION: This patient has a unique pairing of congenital dyserythropoietic anemia and a myeloproliferative disorder. No archival tissue is available so it is impossible to be certain she did not have the JAK2 V617F mutation on initial presentation, although the normal platelet and white blood count at age 6 support the inference that the myeloproliferative disorder arose later. Among patients with essential thrombocythemia, those who have the JAK2 V617F mutation tend to have higher hemoglobin levels, though in her case the development of the JAK2 V617F mutation did not lead to amelioration of her anemia. We hypothesize that the hematopoietic failure state associated with CDA may, like that of myelodysplasia, create an environment in which a genetically-mediated proliferative advantage due to an acquired mutation may be especially favored, and may thus have been a factor in the development of the myeloproliferative disorder.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.003 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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".