Cytokine profiles in polycythemia vera and essential thrombocythemia patients: clinical implications.
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.
Cellular Hematology Laboratory, Département d'Hématologie, Onco-Génétique et Immunologie, Institut de Biologie et Pathologie, Centre Hospitalier Universitaire, Grenoble, France; Thérapies Recombinantes Expérimentales/Techniques de l'Ingénierie Médicale et de la Complexité-Informatique, Mathématiques et Applications, UMR CNRS 5525, Joseph Fourier University, Grenoble, France. Electronic address: epourcelot@chu-grenoble.fr.
Emmanuel
E
Pourcelot
Biochemistry and Enzymology Laboratory, Département de Biochimie, Toxicologie et Pharmacologie, Institut de Biologie et Pathologie, Centre Hospitalier Universitaire, Grenoble, France.
Candice
C
Trocme
Cellular Hematology Laboratory, Département d'Hématologie, Onco-Génétique et Immunologie, Institut de Biologie et Pathologie, Centre Hospitalier Universitaire, Grenoble, France; Thérapies Recombinantes Expérimentales/Techniques de l'Ingénierie Médicale et de la Complexité-Informatique, Mathématiques et Applications, UMR CNRS 5525, Joseph Fourier University, Grenoble, France.
Julie
J
Mondet
Parasitology Laboratory, Département des Agents Infectieux, Institut de Biologie et Pathologie, Centre Hospitalier Universitaire, Grenoble, France.
Sébastien
S
Bailly
Thérapies Recombinantes Expérimentales/Techniques de l'Ingénierie Médicale et de la Complexité-Informatique, Mathématiques et Applications, UMR CNRS 5525, Joseph Fourier University, Grenoble, France; Biochemistry and Enzymology Laboratory, Département de Biochimie, Toxicologie et Pharmacologie, Institut de Biologie et Pathologie, Centre Hospitalier Universitaire, Grenoble, France.
Bertrand
B
Toussaint
Cellular Hematology Laboratory, Département d'Hématologie, Onco-Génétique et Immunologie, Institut de Biologie et Pathologie, Centre Hospitalier Universitaire, Grenoble, France; Thérapies Recombinantes Expérimentales/Techniques de l'Ingénierie Médicale et de la Complexité-Informatique, Mathématiques et Applications, UMR CNRS 5525, Joseph Fourier University, Grenoble, France.
Pascal
P
Mossuz
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011087:Polycythemia Vera / Q000097:blood / Q000235:genetics; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood* / Q000235:genetics
D016207:Cytokines; C507924:JAK2 protein, human; D053614:Janus Kinase 2