Philadelphia-negative myeloproliferative neoplasms as disorders marked by cytokine modulation

Abstract

BackgroundCytokines are key immune mediators in physiological and disease processes, whose increased levels have been associated with the physiopathology of hematopoietic malignancies, such as myeloproliferative neoplasms.MethodsThis study examined the plasma cytokine profiles of patients with essential thrombocythemia, primary myelofibrosis, polycythemia vera and of healthy subjects, and analyzed correlations with JAK2 V617F status and clinical-hematological parameters.ResultsThe proinflammatory cytokine levels were increased in myeloproliferative neoplasm patients, and the presence of the JAK2 V617F mutation was associated with high IP-10 levels in primary myelofibrosis patients.ConclusionsEssential thrombocythemia, primary myelofibrosis, and polycythemia vera patients exhibited different patterns of cytokine production, as revealed by cytokine network correlations. Together, these findings suggest that augmented cytokine levels are associated with the physiopathology of myeloproliferative neoplasms.

The Nlrp3 inflammasome as a “rising star” in studies of normal and malignant hematopoiesis

“…MPN are related to, and may evolve into, MDS or acute myeloid leukemia. It has been demonstrated that the MPN neoplastic clone drives this inflammatory reaction [108][109][110]. To support this, allogeneic stem cell transplantation leads not only to a complete restore of the hematopoiesis, regression of BM fibrosis, and a progressive healing of the chronic inflammation.…”

“…To support this, allogeneic stem cell transplantation leads not only to a complete restore of the hematopoiesis, regression of BM fibrosis, and a progressive healing of the chronic inflammation. Although chronic inflammation in BM microenvironment can be present before a malignant clone develops, most likely it represents a consequence of presence of malignant clone [109][110][111]. It is no doubt that Nlrp3 inflammasome plays an important role in pathogenesis and progression of MPN, however more detailed studies are needed to better address its role in this disorders, as it has been done already in case of MDS [106,107].…”

MPL W515 L/K mutations in myeloproliferative neoplasms

“…In this study, our MPN patients showed a much lower median age at diagnosis of 49.5, 45, and 56.5 in PV, ET, and PMF, respectively, compared with other studies which had a higher median age of 59, 55, and 65 in PV, ET, and PMF, respectively [29][30][31]. This study revealed lower frequency of Jak2 p. Val617Phe pathological variant across PV and PMF represented in 64.3 and 30%, respectively, when compared to other data worldwide for the incidence of Jak2 p. Val617Phe pathological variant which was represented in 85 and 65.8% [13], 81.4 and 46.1% [32], 87.2 and 50% [2], 100% and 68% [33], and 90 and 62% [19] of PV and PMF, respectively.…”

Inflammatory picture of Philadelphia-negative myeloproliferative neoplasms

“…In this issue of the Hematology, Transfusion and Cell Therapy Journal, Cacemiro et al evaluated the plasma cytokine profile of 47 patients with Ph-negative myeloproliferative neoplasms (MPN) [essential thrombocythemia (ET), primary myelofibrosis (PMF), and polycythemia vera (PV)] and of healthy subjects. 1 They demonstrated increased levels of pro-inflammatory cytokines in MPN patients and higher levels of interferon (IFN)-γ-induced protein 10 (IP-10) in PMF patients with the JAK2 V617F mutation. They found differences in the cytokine profile among the three MPN disorders, including increased levels of IL-12p70, IL-17A, and RANTES in PMF, showing that MPN, in particular PMF, have altered inflammatory profiles.…”