Environmental, Lifestyle Risk Factors and Host Characteristics Associated with Philadelphia Negative Myeloproliferative Neoplasm: A Systematic Review
Bibliographic record
Abstract
Abstract Introduction: Myeloproliferative Neoplasms (MPNs) are group of clonal hematopoietic stem cell (HSC) disorders characterised by overproduction of myeloid cells and are associated with an acquired genetic mutation of JAK2V617F. The 2008 WHO MPNs classification grouped the related disorders naming them Philadelphia negative MPNs. These included polycythemia vera, essential thrombocythemia, pre-fibrotic myelofibrosis and primary myelofibrosis which are the focus of this review. The etiology of MPNs remains unknown. Epidemiological studies have indicated there are associations between environmental, lifestyle factors and host characteristic with pathogenesis of MPNs. The aim of this review is to summarize all published data investigating smoking, obesity, gender and exposure to benzene as contributing risk factors and establish their association with developing MPNs. Methods: Medline, Embase, Pubmed databases were systematically searched for relevant published articles with date restrictions of March 2003 to March 2020. The published studies using epidemiological study designs i.e. case control, cohort and cross-sectional studies were identified. Scanning of reference lists and the grey literature was also undertaken. Articles written in English language were included. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Manual review of filtered records excluded inappropriate publications. Two investigators evaluated the full text of selected articles independently analysed the content qualitatively using the Newcastle-Ottawa Scale. Results: A total of 23 published articles met the inclusion criteria, reporting data on the impact of smoking and obesity, the effects of exposure to benzene and gender on MPNs pathogenesis. A significant association was found between smoking and development of MPNs explained by the substantial increase in the levels of several proinflammatory mediators and systematic oxidative stress causing hyperstimulation of myeloid compartments. The upregulation of JAK-STAT and NF-kB signalling pathway and several transcription factors in patients with MPNs who smokers are have been confirmed. Subsequently, these changes facilitate the clonal expansion of hematopoietic stem cells with JAK2V617F mutations. The literature did not confirm any significant association between obesity and risk of developing MPNs, but it cannot be ruled out as an contributing risk factor. The consequences of obesity have been explained in terms of changes in metabolic, endocrinologic, immunologic, and inflammatory systems which may lead to increase in the cell proliferation, cell mutation rate, dysregulate gene function, disturb DNA repair or induce epigenetic changes favouring the induction of neoplastic transformation. There is some evidence in the literature that in individuals exposed to benzene, there is a stimulation of erythropoietic progenitor cells with cytokine independent growth compared to non-exposed individuals. This spontaneous growth of erythroid progenitor cells is one of the hallmarks of MPNs but evidence to prove this hypothesis is uncertain. No strong association was found between exposure of benzene and MPNs but further investigation on effects of increased levels and duration of exposure will be beneficial. Host characteristics such as gender as contributing factors associated with MPNs has been explored in several studies. Gender has been classified as an independent modifier in JAK2V617F allele burden which influences genotype and clonal expansion resulting into allele burden variability, hence, partly responsible for to the differences in the development of the disease between males and females. Conclusion: The important role of predisposing factors such as environmental, lifestyle risk factors and host characteristic in the pathogenesis of MPNs cannot be eliminated. The significant association between smoking and developing MPNs has been confirmed. Gender can be classified as an independent modifier in JAK2V617F allele burden reflecting on the phenotypic heterogeneity of MPNs. The relationship between obesity and exposure to benzene with MPNs developments has not been established yet. The results from this review proposes a large, well-designed epidemiological research exploring these contributing factors. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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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 | 0.004 | 0.015 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.007 | 0.007 |
| Bibliometrics | 0.009 | 0.013 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".