Cytokine profiles in polycythemia vera and essential thrombocythemia patients: Clinical implications
Open accessAbstract
Studies have shown that the clinical impact of Janus kinase 2 (JAK2) inhibitors in primary myelofibrosis patients is due to the regulation of cytokine levels, suggesting that cytokine profiles might play a critical role in myeloproliferative neoplasms (MPNs) physiopathology. In this study, we compared the plasma cytokine profiles of polycythemia vera (PV) patients and essential thrombocythemia (ET) patients as a function of their JAK2 V617F status and the presence of thrombohemorrhagic complications. Using a multiplex cytokine assay, cytokine measurements were taken of the plasma of 17 PV patients and 21 ET patients. Twenty-two of these patients (10 PV and 12 ET) experienced at least one thrombohemorrhagic manifestation before diagnosis. We showed that cytokine levels were significantly increased in PV and ET patients compared with normal values and that several positive correlations existed between the cytokine concentrations and the biological parameters in each MPN. The comparison between the cytokine profiles of ET and PV patients showed a statistically significant increase of interleukin (IL)-4, IL-8, granulocyte macrophage-colony stimulating factor, interferon -γ, monocyte chemotactic protein -1, platelet derived growth factor-BB, and vascular endothelial growth factor in the ET group. Only tumor necrosis factor-α and platelet derived growth factor-BB were specifically impacted by the JAK2 V617F status of the PV and ET patients, respectively, suggesting that there are both JAK2 V617F-driven and JAK2 V617F-independent inflammatory responses in MPNs. We also showed that the subgroup of PV patients with vascular complications displayed significantly different concentrations of IL-12(p70) and granulocyte macrophage-colony stimulating factor compared with patients without vascular complications. Altogether, these data suggest that cytokine measurement might be useful for the clinical and therapeutic stratification of PV and ET patients.
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The individual datasets, together with the baseline ET samples from our previous work, were integrated and underwent batch correction within Seurat.
“These individual datasets, together with the baseline ET samples from our previous work 20 , were integrated and underwent batchcorrection within Seurat”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [20]
The Patients and sample preparation section (page unavailable) reports samples from 21 patients with essential thrombocythemia, supporting the citation’s identification of earlier ET samples. But the paper describes plasma cytokine measurements, not baseline ET datasets that could be integrated in Seurat; its Statistical analysis section (page unavailable) names other software and does not describe batch correction. (LLM, conf=0.78)
Experimental — accuracy not yet measuredMPN megakaryocytes exhibit higher expression of TGFB1.
“We and others have shown that MPN megakaryocytes indeed exhibit higher expression of TGFB1 20,50,51 , and thus downregulation of TGFB1 by IFNa may be a key mechanism of improvement in fibrosis frequently observed in patients treated with IFNa.”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [20]
The Methods section lists the 13 plasma cytokines measured, but TGFB1 is not among them. The Discussion links megakaryocytes to PDGF-BB synthesis, not to higher TGFB1 expression. Searches for TGFB1 and transforming growth factor beta found no passage addressing the attributed claim; page numbers were unavailable in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredDownregulation of TGFB1 by IFNa may be a key mechanism of improvement in fibrosis frequently observed in patients treated with IFNa.
“We and others have shown that MPN megakaryocytes indeed exhibit higher expression of TGFB1 20,50,51 , and thus downregulation of TGFB1 by IFNa may be a key mechanism of improvement in fibrosis frequently observed in patients treated with IFNa.”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [20]
The citation is attached to the statement that MPN megakaryocytes have higher TGFB1 expression, but the indexed paper does not address TGFB1 expression. Its cytokine-assay methods list IFN-gamma, not IFN-alpha or TGFB1; the treatment discussion concerns JAK inhibitors, not IFN-alpha or fibrosis improvement. Searches for TGFB1 in megakaryocytes and for IFN-alpha–related fibrosis found no supporting passage. The proposed mechanism after the citation is the citing authors’ inference. (LLM, conf=0.76)
Experimental — accuracy not yet measuredThese findings contrasted with the more subtle transcriptional impact of CALR-mutations, since mutated and wildtype cells are co-mingled throughout differentiation.
“These findings contrasted with the more subtle transcriptional impact of CALR -mutations, since mutated and wildtype cells are co-mingled throughout differentiation 20,39 .”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [20]
The Discussion and “Impact of JAK2 status” sections address JAK2 V617F and cytokine profiles, not CALR mutations. Searches for CALR, transcriptional effects, and co-mingling of mutant and wild-type cells during differentiation found no passage addressing the claim. Page numbers were not available in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredCALR mutations enhance the unfolded protein response, specifically the pro-survival IRE1-XBP1 axis.
“CALR mutations enhance the unfolded protein response (UPR), specifically the pro-survival IRE1-XBP1 axis 20”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [20]
The Discussion (page unavailable) describes cytokine profiling in polycythemia vera and essential thrombocythemia, including responses associated with JAK2 V617F. Searches for CALR mutations, the unfolded protein response, and IRE1-XBP1 found no passage in our copy addressing the claimed mechanism. (LLM, conf=0.78)
Experimental — accuracy not yet measured
At baseline, the CALR-mutation induced proliferation in the HSCs and the myeloid cell lineages (i.e. the granulo-monocytic and megakaryocytic-erythroid lineages) but not in the lymphoid progenitors.
“At baseline, the CALR -mutation induced proliferation in the HSCs and the myeloid cell lineages (i.e. the granulo-monocytic and megakaryocytic-erythroid lineages) but not in the lymphoid progenitors ( Fig. 3e ), consistent with our previous reporting 20 .”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [20]
The paper’s discussion addresses cytokine profiles and JAK2 V617F in polycythemia vera and essential thrombocythemia, not CALR-driven proliferation. Searches for CALR, hematopoietic stem cells, myeloid lineages, and lymphoid progenitors found no passage addressing the claimed lineage-specific effect; page numbers were unavailable in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredMutated and wildtype HSPCs were co-mingled throughout differentiation both at baseline and upon IFNa therapy.
“Consistent with our previous results 20 , the mutated and wildtype HSPCs were co-mingled throughout differentiation both at baseline and upon IFNa therapy ( Fig. 3a, Supplementary Fig. 5a) .”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [20]
The Impact of JAK2 status section compares plasma cytokine concentrations in JAK2 V617F-positive and -negative patients, not the positions of mutated and wildtype HSPCs during differentiation. Searches for co-mingling, HSPC differentiation, and IFNα therapy found no passage addressing the claim; the paper’s interferon measurement concerns IFN-γ. (LLM, conf=0.76)
Experimental — accuracy not yet measured
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Research works printed but not linked: 27
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Cited by
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Inflammatory Pathophysiology as a Contributor to Myeloproliferative Neoplasms
Fisher, D. A. C., Fowles, J. S., Zhou, A., & Oh, S. T. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.683401 · Cited by 115 · see citing works
Type 1 interferon perturbates clonal competition by reshaping human blood development
Lama, C., Isakov, D., Rosenberg, S., Quijada-Álamo, M., Saurty-Seerunghen, M. S., Moein, S., Nozais, M., Abera, T.-A., Sakaguchi, O., Totwani, M., et al. (2026) · Nature Genetics · doi:10.1038/s41588-026-02751-3 · Cited by 3 · see citing works
- Authors
- Pourcelot, E., Trocme, C., Mondet, J., Bailly, S., Toussaint, B., & Mossuz, P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Centre Hospitalier Universitaire de Grenoble (FR)
- Corresponding author
- Pourcelot, Emmanuel
- Venue
- Experimental Hematology
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 42
- Issue
- 5
- Pages
- 360-368
- ISSN
- 0301-472X (ISSN-L)
- OpenAlex
- W2134290384
- Cited by
- 132
- References
- 0
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 15 · 2023: 7 · 2022: 10 · 2021: 20 · 2020: 14 · 2019: 12 · 2018: 13 · 2017: 8 · 2016: 7 · 2015: 10 · 2014: 2
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Experimental Hematology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Myeloproliferative Neoplasms: Diagnosis and Treatment
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Medicine › Emergency Medicine › Hematological disorders and diagnostics
- Keywords
- polycythemia vera, essential thrombocythemia, cytokine profile, JAK2 V617F mutation, myeloproliferative neoplasms, thrombohemorrhagic complications, vascular complications, IL-4, interleukin-8, GM-CSF, interferon-gamma, MCP-1, PDGF-BB, vascular endothelial growth factor, TNF-α, inflammation, JAK2 inhibitors
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Polycythemia Vera, Cytokines, Purpura, Thrombocytopenic, Idiopathic, Amino Acid Substitution, Mutation, Missense, Janus Kinase 2
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