Disease-Specific Derangement of Circulating Endocannabinoids and N-Acylethanolamines in Myeloproliferative Neoplasms.

Growing evidence highlights the endocannabinoid (EC) system involvement in cancer progression. Lipid mediators of this system are secreted by hematopoietic cells, including the ECs 2-arachidonoyl-glycerol (2AG) and arachidonoyl-ethanolamide (AEA), the 2AG metabolite 1AG, and members of N-acylethanolamine (NAE) family-palmitoyl-ethanolamide (PEA) and oleoyl-ethanolamide (OEA). However, the relevance of the EC system in myeloproliferative neoplasms (MPN) was never investigated. We explored the EC plasma profile in 55 MPN patients, including myelofibrosis (MF; n = 41), polycythemia vera (PV; n = 9), and essential thrombocythemia (ET; n = 5) subclasses and in 10 healthy controls (HC). AEA, PEA, OEA, 2AG, and 1AG plasma levels were measured by LC-MS/MS. Overall considered, MPN patients displayed similar EC and NAE levels compared to HC. Nonetheless, AEA levels in MPN were directly associated with the platelet count. MF patients showed higher levels of the sum of 2AG and 1AG compared to ET and PV patients, higher OEA/AEA ratios compared to HC and ET patients, and higher OEA/PEA ratios compared to HC. Furthermore, the sum of 2AG and 1AG positively correlated with JAK2V617F variant allele frequency and splenomegaly in MF and was elevated in high-risk PV patients compared to in low-risk PV patients. In conclusion, our work revealed specific alterations of ECs and NAE plasma profile in MPN subclasses and potentially relevant associations with disease severity.

Mobilized Peripheral Blood versus Cord Blood: Insight into the Distinct Role of Proinflammatory Cytokines on Survival, Clonogenic Ability, and Migration of CD34+ Cells.

Inflammation may play a role in cancer. However, the contribution of cytokine-mediated crosstalk between normal hemopoietic stem/progenitor cells (HSPCs) and their (inflammatory) microenvironment is largely elusive. Here we compared survival, phenotype, and function of neonatal (umbilical cord blood (CB)) and adult (normal G-CSF-mobilized peripheral blood (mPB)) CD34+ cells after in vitro exposure to combined crucial inflammatory factors such as interleukin- (IL-) 1ß, IL-6, tumor necrosis factor- (TNF-) α, or tissue inhibitor of metalloproteinases-1 (TIMP-1). To mimic bone marrow (BM) niche, coculture experiments with normal BM stromal cells (BMSCs) were also performed. We found that combined inflammatory cytokines increased only the in vitro survival of CB-derived CD34+ cells by reducing apoptosis. Conversely, selected combinations of inflammatory cytokines (IL-1ß + TNF-α, IL-6 + TNF-α, and IL-1ß + TNF-α + TIMP-1) mainly enhanced the in vitro CXCR4-driven migration of mPB-derived CD34+ cells. TNF-α, alone or in combination, upregulated CD44 and CD13 expression in both sources. Finally, BMSCs alone increased survival/migration of CB- and mPB-derived CD34+ cells at the same extent of the combined inflammatory cytokines; importantly, their copresence did not show additive/synergistic effect. Taken together, these data indicate that combined proinflammatory stimuli promote distinct in vitro functional activation of neonatal or adult normal HSPCs.

Pain during Rapid Maxillary Expansion: A Systematic Review.

AIM: The aim of the present systematic review is to evaluate the pain perceived by patients during rapid maxillary expansion (RME) in relation to factors such as demographic characteristics, appliance type, activation protocol, and the eventual use of medication or pain management strategies. MATERIALS AND METHODS: An electronic search of available articles on the subject was conducted on three electronic databases, using predefined keywords. Sequential screenings based on pre-established eligibility criteria were performed. RESULTS: Ten studies were ultimately included in this systematic review. The main data of the reviewed studies were extracted according to the PICOS approach. CONCLUSIONS: Pain is a common effect of RME treatment that tends to decrease over time. Gender and age differences in pain perception are not clear. Perceived pain is influenced by the expander design and expansion protocol used. Some pain management strategies can be useful for reducing RME-associated pain.

A Multiparameter Prognostic Risk Score of Chronic Graft-versus-Host Disease Based on CXCL10 and Plasmacytoid Dendritic Cell Levels in the Peripheral Blood at 3 Months after Allogeneic Hematopoietic Stem Cell Transplantation.

Chronic GVHD (cGVHD) is the major cause of long-term morbidity after allogeneic hematopoietic stem cell transplantation (HSCT). There are no biomarkers that can consistently predict its occurrence. We aimed to evaluate whether numbers of antigen-presenting cell subsets in peripheral blood (PB) or serum chemokine concentrations are biomarkers of cGVHD occurrence. The study cohort comprised 101 consecutive patients undergoing allogeneic HSCT between January 2007 and 2011. cGVHD was diagnosed by both modified Seattle criteria and National Institutes of Health (NIH) criteria. Multicolor flow cytometry was used to determine the number of PB myeloid dendritic cells (DCs), plasmacytoid DCs, CD16+ DCs, and CD16+ and CD16- monocytes, as well as CD4+ and CD8+ T cells, CD56+ natural killer cells, and CD19+ B cells. Serum concentrations of CXCL8, CXCL10, CCL2, CCL3, CCL4, and CCL5 were measured by a cytometry bead array assay. At a median of 60 days after enrollment, 37 patients had developed cGVHD. Patients with cGVHD and those without cGVHD had comparable clinical characteristics. However, previous acute GVHD (aGVHD) was strongly correlated with later cGVHD (57% versus 24%, respectively; P = .0024). Each potential biomarker was screened for its association with cGVHD using the Mann-Whitney U test. Biomarkers that differed significantly (P < .05) between patients with cGVHD and those without cGVHD were analyzed by receiver operating characteristic (ROC) curve analysis to select the variables predicting cGVHD with an area under the ROC curve (AUC) >.5 and a P value <.05. A multivariate Fine-Gray model identified the following variables as independently associated with the risk of cGVHD: CXCL10 ≥592.650 pg/mL (hazard ratio [HR], 2.655; 95% confidence interval [CI], 1.298 to 5.433; P = .008), pDC ≥2.448/µL (HR, .286; 95% CI, .142 to .577; P < .001) and previous aGVHD (HR, 2.635; 95% CI, 1.298 to 5.347; P = .007). A risk score was derived based on the weighted coefficients of each variable (2 points each), resulting in the identification of 4 cohorts of patients (scores of 0, 2, 4, and 6). In a competing risk analysis to stratify patients at differing risk levels of cGVHD, the cumulative incidence of cGVHD was 9.7%, 34.3%, 57.7%, and 100% in patients with scores of 0, 2, 4, and 6, respectively (P < .0001). The score could nicely stratify the patients based on the risk of extensive cGVHD as well as NIH-based global and moderate to severe cGVHD. Based on ROC analysis, the score could predict the occurrence of cGVHD with an AUC of .791 (95% CI, .703 to .880; P < .001). Finally, a cutoff score ≥4 was identified as the optimal cutoff by Youden J index with a sensitivity of 57.1% and a specificity of 85.0%. A multiparameter score including a history of previous aGVHD, serum CXCL10 concentration, and number of pDCs in the PB at 3 months post-HSCT stratify patients at varying risk levels of cGVHD. However, the score needs to be validated in a much larger independent and possibly multicenter cohort of patients undergoing transplantation from different donor types and with distinct GVHD prophylaxis regimens.

The Accuracy of Jaws Repositioning in Bimaxillary Orthognathic Surgery in Patients with Cleft Lip and Palate Compared to Non-Syndromic Skeletal Class III Patients.

Background: The present study aims to compare the accuracy of jaw repositioning in bimaxillary orthognathic surgery using digital surgical planning in cleft lip and palate patients and in non-syndromic skeletal class III patients in order to investigate if orthognathic surgery achieves different results in the first group of patients. Method: This study included 32 class III adult patients divided into 2 groups: cleft lip and palate (A, n = 16) and non-cleft (B, n = 16). For each patient, a 2D pre-surgical visual treatment objective was performed by the surgeon to predict hard tissue changes, and the surgical outcome was compared with that planned by using cephalometric measurement (ANB, SNA, SNB, Ar-Go-Me, S-Ar-Go). The statistical analysis showed equivalence between obtained and planned results for each measurement both in group A and in group B, but the difference between the planned and the obtained result was smaller in group B regarding ANB angle. Conclusions: Digital surgical planning ensures better predictability of the surgical results and higher accuracy of surgery in complex patients, such as those with cleft lip and palate.

The validity of panoramic radiograph as a diagnostic method for elongated styloid process: A systematic review.

Objective: To evaluate the validity of panoramic radiograph as a radiographic method for the diagnosis of an elongated styloid process (ESP) in the general population.Methods: An electronic search of available articles about ESP was conducted on PubMed. Sequential screenings based on previously defined exclusion and inclusion criteria were performed.Results: Eight studies were included in the systematic review. Prevalence of ESP and mean radiological length of the styloid process (SP) increased with age, which might be due to a chronic calcification development of the SP. Most of the included studies also asserted that there was no statistically significant correlation between ESP and the gender.Discussion: Panoramic radiograph is easy to perform and interpret, so it can be defined as being useful for diagnosis of ESP in the general population. In symptomatic patients, it can help in the differential diagnosis with other conditions associated with orofacial and neck pain.

Validation of Vectra 3D Imaging Systems: A Review.

Aim: Three-dimensional facial imaging systems are a useful tool that is gradually replacing two-dimensional imaging and traditional anthropometry with calipers. In this varied and growing landscape of new devices, Canfield (Canfield Scientific, Parsippany, NJ, USA) has proposed a series of static and portable 3D imaging systems. The aim of this systematic review was to evaluate the current literature regarding the validation of Canfield's Vectra imaging systems. Materials and Methods: A search strategy was developed on electronic databases including PubMed, Web of Science and Scopus by using specific keywords. After the study selection phase, a total of 10 articles were included in the present review. Results: A total of 10 articles were finally included in the present review. For six articles, we conducted a validation of the Vectra static devices, focusing especially on the Vectra M5, Vectra M3 and Vectra XT. For four articles, we validated the Vectra H1 portable system. Conclusions: All of the reviewed articles concluded that Canfield's Vectra 3D imaging systems are capable of capturing accurate and reproducible stereophotogrammetric images. Minor errors were reported, particularly in the acquisition of the perioral region, but all the evaluated devices are considered to be valid and accurate tools for clinicians.

The ALLgorithMM: How to define the hemodilution of bone marrow samples in lymphoproliferative diseases.

Introduction: Minimal residual disease (MRD) is commonly assessed in bone marrow (BM) aspirate. However, sample quality can impair the MRD measurement, leading to underestimated residual cells and to false negative results. To define a reliable and reproducible method for the assessment of BM hemodilution, several flow cytometry (FC) strategies for hemodilution evaluation have been compared. Methods: For each BM sample, cells populations with a well-known distribution in BM and peripheral blood - e.g., mast cells (MC), immature (IG) and mature granulocytes (N) - have been studied by FC and quantified alongside the BM differential count. Results: The frequencies of cells' populations were correlated to the IG/N ratio, highlighting a mild correlation with MCs and erythroblasts (R=0.25 and R=0.38 respectively, with p-value=0.0006 and 0.0000052), whereas no significant correlation was found with B or T-cells. The mild correlation between IG/N, erythroblasts and MCs supported the combined use of these parameters to evaluate BM hemodilution, hence the optimization of the ALLgorithMM. Once validated, the ALLgorithMM was employed to evaluate the dilution status of BM samples in the context of MRD assessment. Overall, we found that 32% of FC and 52% of Next Generation Sequencing (NGS) analyses were MRD negative in samples resulted hemodiluted (HD) or at least mildly hemodiluted (mHD). Conclusions: The high frequency of MRD-negative results in both HD and mHD samples implies the presence of possible false negative MRD measurements, impairing the correct assessment of patients' response to therapy and highlighs the importance to evaluate BM hemodilution.

The "Vesicular Intelligence" Strategy of Blood Cancers.

Blood cancers are a heterogeneous group of disorders including leukemia, multiple myeloma, and lymphoma. They may derive from the clonal evolution of the hemopoietic stem cell compartment or from the transformation of progenitors with immune potential. Extracellular vesicles (EVs) are membrane-bound nanovesicles which are released by cells into body fluids with a role in intercellular communication in physiology and pathology, including cancer. EV cargos are enriched in nucleic acids, proteins, and lipids, and these molecules can be delivered to target cells to influence their biological properties and modify surrounding or distant targets. In this review, we will describe the "smart strategy" on how blood cancer-derived EVs modulate tumor cell development and maintenance. Moreover, we will also depict the function of microenvironment-derived EVs in blood cancers and discuss how the interplay between tumor and microenvironment affects blood cancer cell growth and spreading, immune response, angiogenesis, thrombogenicity, and drug resistance. The potential of EVs as non-invasive biomarkers will be also discussed. Lastly, we discuss the clinical application viewpoint of EVs in blood cancers. Overall, blood cancers apply a 'vesicular intelligence' strategy to spread signals over their microenvironment, promoting the development and/or maintenance of the malignant clone.

Orthodontic, Maxillofacial Surgery, and Prosthodontic Rehabilitation Supported by Miniscrew in a Patient with Cleft Lip and Palate.

Aim. This paper is aimed at reporting the clinical case of a patient with cleft lip and palate treated with a multidisciplinary approach. Case Report. An 11-year-old patient presented cleft lip and palate, with persistent oronasal communication, tooth displacement, and upper and lower crowding with a deep curve of Spee. He was treated with metal bracket orthodontic therapy, graft surgery, and prosthetic rehabilitation supported by miniscrews. Conclusions. Cleft lip and/or palate patients require adequate management of the case to resolve the anomalies connected to their condition and to improve their quality of life.

A Specific Host/Microbial Signature of Plasma-Derived Extracellular Vesicles Is Associated to Thrombosis and Marrow Fibrosis in Polycythemia Vera.

Polycythemia vera is a myeloproliferative neoplasm with increased risk of thrombosis and progression to myelofibrosis. However, no disease-specific risk factors have been identified so far. Circulating extracellular vesicles (EVs) are mostly of megakaryocyte (MK-EVs) and platelet (PLT-EVs) origin and, along with phosphatidylethanolamine (PE)-EVs, play a role in cancer and thrombosis. Interestingly, circulating microbial components/microbes have been recently indicated as potential modifiers of inflammation and coagulation. Here, we investigated phenotype and microbial DNA cargo of EVs after isolation from the plasma of 38 patients with polycythemia vera. Increased proportion of MK-EVs and reduced proportion of PLT-EVs identify patients with thrombosis history. Interestingly, EVs from patients with thrombosis history were depleted in Staphylococcus DNA but enriched in DNA from Actinobacteria members as well as Anaerococcus. In addition, patients with thrombosis history had also lower levels of lipopolysaccharide-associated EVs. In regard to fibrosis, along with increased proportion of PE-EVs, the EVs of patients with marrow fibrosis were enriched in DNA from Collinsella and Flavobacterium. Here, we identified a polycythemia-vera-specific host/microbial EV-based signature associated to thrombosis history and marrow fibrosis. These data may contribute to refining PV prognosis and to identifying novel druggable targets.

An Abnormal Host/Microbiomes Signature of Plasma-Derived Extracellular Vesicles Is Associated to Polycythemia Vera.

Polycythemia Vera (PV) is a myeloproliferative neoplasm with increased risk of thrombosis and progression to myelofibrosis. Chronic inflammation is commonly observed in myeloproliferative neoplasms including PV. The inflammatory network includes the extracellular vesicles (EVs), which play a role in cell-cell communication. Recent evidence points to circulating microbial components/microbes as potential players in hemopoiesis regulation. To address the role of EVs in PV, here we investigated phenotype and microbial DNA cargo of circulating EVs through multidimensional analysis. Peripheral blood and feces were collected from PV patients (n=38) and healthy donors (n=30). Circulating megakaryocyte (MK)- and platelet (PLT)-derived EVs were analyzed by flow cytometry. After microbial DNA extraction from feces and isolated EVs, the 16S rDNA V3-V4 region was sequenced. We found that the proportion of circulating MK-derived EVs was significantly decreased in PV patients as compared with the healthy donors. By contrast, the proportion of the PLT-derived EVs was increased. Interestingly, PV was also associated with a microbial DNA signature of the isolated EVs with higher diversity and distinct microbial composition than the healthy counterparts. Of note, increased proportion of isolated lipopolysaccharide-associated EVs has been demonstrated in PV patients. Conversely, the gut microbiome profile failed to identify a distinct layout between PV patients and healthy donors. In conclusion, PV is associated with circulating EVs harbouring abnormal phenotype and dysbiosis signature with a potential role in the (inflammatory) pathogenesis of the disease.

Distinct profile of CD34+ cells and plasma-derived extracellular vesicles from triple-negative patients with Myelofibrosis reveals potential markers of aggressive disease.

BACKGROUND: Myelofibrosis (MF) is a clonal disorder of hemopoietic stem/progenitor cells (HSPCs) with high prevalence in elderly patients and mutations in three driver genes (JAK2, MPL, or CALR). Around 10-15% of patients are triple-negative (TN) for the three driver mutations and display significantly worse survival. Circulating extracellular vesicles (EVs) play a role in intercellular signaling and are increased in inflammation and cancer. To identify a biomolecular signature of TN patients, we comparatively evaluated the circulating HSPCs and their functional interplay with the microenvironment focusing on EV analysis. METHODS: Peripheral blood was collected from MF patients (n = 29; JAK2V617F mutation, n = 23; TN, n = 6) and healthy donors (HD, n = 10). Immunomagnetically isolated CD34+ cells were characterized by gene expression profiling analysis (GEP), survival, migration, and clonogenic ability. EVs were purified from platelet-poor plasma by ultracentrifugation, quantified using the Nanosight technology and phenotypically characterized by flow cytometry together with microRNA expression. Migration and survival of CD34+ cells from patients were also analyzed after in vitro treatments with selected inflammatory factors, i.e. (Interleukin (IL)-1ß, Tumor Necrosis Factor (TNF)-α, IL6) or after co-culture with EVs from MF patients/HD. RESULTS: The absolute numbers of circulating CD34+ cells were massively increased in TN patients. We found that TN CD34+ cells show in vitro defective functions and are unresponsive to the inflammatory microenvironment. Of note, the plasma levels of crucial inflammatory cytokines are mostly within the normal range in TN patients. Compared to JAK2V617F-mutated patients, the GEP of TN CD34+ cells revealed distinct signatures in key pathways such as survival, cell adhesion, and inflammation. Importantly, we observed the presence of mitochondrial components within plasma EVs and a distinct phenotype in TN-derived EVs compared to the JAK2V617F-mutated MF patients and HD counterparts. Notably, TN EVs promoted the survival of TN CD34+ cells. Along with a specific microRNA signature, the circulating EVs from TN patients are enriched with miR-361-5p. CONCLUSIONS: Distinct EV-driven signals from the microenvironment are capable to promote the TN malignant hemopoiesis and their further investigation paves the way toward novel therapeutic approaches for rare MF.

Fournier's gangrene during lenvatinib treatment: A case report.

Fournier's gangrene is a rare and severe complication reported in patients with cancer treated with antiangiogenic drugs, most frequently with bevacizumab. The present report describes the case of an 80-year-old man with radioactive iodine-refractory metastatic thyroid cancer treated with lenvatinib (an oral multikinase inhibitor with antiangiogenic properties) who developed Fournier's gangrene in the absence of other known risk factors. To the best of our knowledge, this is the first case described during treatment with lenvatinib. The condition was likely due to a perturbation of vascular endothelial cells of the skin due to the inhibition of VEGF/VEGFR signaling. Fournier's gangrene may be a class effect of antiangiogenic treatment that clinicians should be aware of, as early diagnosis and treatment are associated with an improved outcome.

The Accuracy of Jaws Repositioning in Bimaxillary Orthognathic Surgery with Traditional Surgical Planning Compared to Digital Surgical Planning in Skeletal Class III Patients: A Retrospective Observational Study.

BACKGROUND: Technological progress has led to the transition to digital methods to perform surgical planning and to obtain surgical splints with CAD/CAM technologies. The present study aimed to compare the accuracy of jaw repositioning in bimaxillary orthognathic surgery using traditional and digital surgical planning in skeletal class III patients. METHODS: This study included 60 skeletal class III patients divided into two groups based on the method used to perform surgical planning: traditional (T, n = 30) and digital (D, n = 30). For each patient, a 2D presurgical Visual Treatment Objective (VTO) was prepared and the outcome of the surgery was compared with that planned by using determined cephalometric measurements (ANB, SNA, SNB, Ar-Go-Me, S-Ar-Go). Statistical analysis showed that the measurements planned and those obtained after surgery were equivalent in Group D. For Group T, the analysis showed equivalence only for one of the considered measurements (ANB). By comparing the results of the two groups, Group D presented a lower level of error than Group T. CONCLUSIONS: Digital surgical planning performed significantly better in terms of accuracy of jaw repositioning than the traditional protocol.

The role of circulating monocytes and JAK inhibition in the infectious-driven inflammatory response of myelofibrosis.

Myelofibrosis (MF) is characterized by chronic inflammation and hyper-activation of the JAK-STAT pathway. Infections are one of the main causes of morbidity/mortality. Therapy with Ruxolitinib (RUX), a JAK1/2 inhibitor, may further increase the infectious risk. Monocytes are critical players in inflammation/immunity through cytokine production and release of bioactive extracellular vesicles. However, the functional behavior of MF monocytes, particularly during RUX therapy, is still unclear. In this study, we found that monocytes from JAK2V617F-mutated MF patients show an altered expression of chemokine (CCR2, CXCR3, CCR5) and cytokine (TNF-α-R, IL10-R, IL1ß-R, IL6-R) receptors. Furthermore, their ability to produce and secrete free and extracellular vesicles-linked cytokines (IL1ß, TNF-α, IL6, IL10) under lipopolysaccharides (LPS) stimulation is severely impaired. Interestingly, monocytes from RUX-treated patients show normal level of chemokine, IL10, IL1ß, and IL6 receptors together with a restored ability to produce intracellular and to secrete extracellular vesicles-linked cytokines after LPS stimulation. Conversely, RUX therapy does not normalize TNF-R1/2 receptors expression and the LPS-driven secretion of free pro/anti-inflammatory cytokines. Accordingly, upon LPS stimulation, in vitro RUX treatment of monocytes from MF patients increases their secretion of extracellular vesicles-linked cytokines but inhibits the secretion of free pro/anti-inflammatory cytokines. In conclusion, we demonstrated that in MF the infection-driven response of circulating monocytes is defective. Importantly, RUX promotes their infection-driven cytokine production suggesting that infections following RUX therapy may not be due to monocyte failure. These findings contribute to better interpreting the immune vulnerability of MF and to envisaging strategies to improve the infection-driven immune response.

Taller-Than-Wide Shape: A New Definition Improves the Specificity of TIRADS Systems.

INTRODUCTION: A taller-than-wide (TTW) shape is a suspicious feature of thyroid nodules commonly defined as an anteroposterior/transverse diameter (AP/T) ratio >1. An intraobserver variability of up to 18% in AP diameter evaluations has been described, which may lead to overreporting of this feature. To potentially improve the reliability of the TTW definition, we propose an arbitrary ratio of ≥1.2. OBJECTIVE: The aim of this study was to estimate the impact of this definition on diagnostic performance. METHODS: We prospectively analyzed 553 thyroid nodules referred for cytology evaluation at an academic center. Before fine-needle aspiration, two examiners jointly defined all sonographic features considered in risk stratification systems developed by the American Thyroid Association (ATA), the American Association of Clinical Endocrinologists (AACE), the American College of Radiology (ACR TIRADS), the European Thyroid Association (EU-TIRADS), and the Korean Society of Thyroid Radiology (K-TIRADS). TTW was defined according to the current definition (AP/T diameter ratio >1) and an arbitrary alternative definition (AP/T ratio >1.2). RESULTS: The alternative definition classified fewer nodules as TTW (28, 5.1% vs. 94, 17%). The current and proposed definitions have a sensitivity of 26.2 and 11.9% (p = 0.03) and a specificity of 83.8 and 95.5% (p < 0.001). Thus, as a single feature, the arbitrary definition has a lower sensitivity and a higher specificity. When applied to sonographic risk stratification systems, however, the proposed definition would increase the number of avoided biopsies (up to 58.2% for ACR TIRADS) and the specificity of all systems, without negative impact on sensitivity or diagnostic odds ratio. CONCLUSIONS: Re-defining TTW nodules as those with an AP/T ratio ≥1.2 improves this marker's specificity for malignancy. Using this definition in risk stratification systems will increase their specificity, reducing the number of suggested biopsies without significantly diminishing their overall diagnostic performance.

Mutations in JAK2 and Calreticulin genes are associated with specific alterations of the immune system in myelofibrosis.

Myelofibrosis (MF) is a clonal neoplasia associated with chronic inflammation due to aberrant cytokine production. Mutations in Janus Kinase-2 (JAK2), calreticulin (CALR) and myeloproliferative leukemia protein (MPL) genes have been recently associated to MF and they all activate the JAK/STAT signaling pathway. Since this pathway is essential in shaping the immune response, we investigated the role of circulating immune subsets and cytokines in 38 patients (20 carrying JAK2(V617F),13 exon-9 CALR mutation and 5 triple negative). In comparison to healthy donors, patients presented a reduced amount of circulating dendritic cells (DCs) associated with a defective ability of monocytes in differentiating into DCs. In addition, we found a reduction in circulating T-helper (Th)1 and Th17 and hypo-functional innate lymphoid cells (ILC). Results analyzed according to the mutational status showed that patients carrying JAK2(V617F) mutation had a reduction in Th17, myeloid-DCs and effector Tregs as well as increased ILC1 and cytokine producing Tregs. The CALR mutated patients revealed high ILC3 levels, reduced Th1 and their monocytes had a reduced capacity to mature in vitro into fully committed DCs. Their Tregs were also less effective in inhibiting the proliferation of autologous effector T-cells due to an increased proliferative status induced by CALR mutation. Triple negative patients presented a reduced amount of total circulating CD3, effectors Tregs and Th1 with increased ILC1. Overall, we have demonstrated that in MF different mutations lead to phenotypic and functional alterations in different immune subsets that may have a potential role in disease progression and susceptibility to infections.