Explore the vast range of titles available.

Background Philadelphia (Ph) chromosome-negative myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematopoietic stem cell clonal diseases. Most patients with MPN are asymptomatic at diagnosis although some of them suffer from constitutional symptoms. Thrombosis and bleeding can also be one of the initial manifestations although the reported prevalence varied considerably across the studies. This systematic review and meta-analysis was conducted with the aims to better understand the prevalence and characteristics of thrombosis and bleeding among patients with newly-diagnosed MPN. Methods Using a search strategy that included the terms for myeloproliferative neoplasms, thrombosis, and bleeding, two investigators independently searched for published articles indexed in the MEDLINE and EMBASE databases from inception to August 2018. The pooled prevalence was calculated using the DerSimonian–Laird random-effects model with a double arcsine transformation. Results A total of 29 cohort studies (8 prospective and 21 retrospective) with 13,436 patients with MPN were included into this meta-analysis. At diagnosis, the pooled prevalence of overall thrombosis among patients with MPN was 20.0% (95% CI, 16.6–23.8%; I 2 96%), with the pooled prevalence of arterial thrombosis of 16.2% (95% CI, 13.0–20.0%; I 2 95%) and the pooled prevalence of venous thrombosis of 6.2% (95% CI, 4.9–7.8%; I 2 89%). Common thrombotic events included cerebrovascular disease/transient ischemic attack, coronary heart disease, and deep venous thrombosis. The pooled prevalence of hemorrhagic complications among patients who were newly diagnosed with MPN patients was 6.2% (95% CI, 5.0–7.8%; I 2 85%). Common sites of bleeding included gastrointestinal, mucosal, and cutaneous bleeding. Conclusions Thrombosis and bleeding are common initial manifestations of MPN. Investigations for MPN should be considered for patients who present with unexplained thrombosis or abnormal bleeding.

The myeloproliferative disorders, comprising polycythemia vera, essential thrombocytosis, and myelofibrosis, are clonal hematopoietic cancers that have an indolent course. The clinical manifestations of these entities overlap, as do their genetic drivers. The myeloproliferative neoplasms — polycythemia vera, essential thrombocytosis, and primary myelofibrosis — are unique hematopoietic stem-cell disorders that share mutations that constitutively activate the physiologic signal-transduction pathways responsible for hematopoiesis (Table 1). Consequently, these disorders engage in phenotypic mimicry among themselves, as well as with myeloid neoplasms and even benign hematopoietic disorders. In contrast to the myeloid neoplasms, the myeloproliferative neoplasms have a natural history, with supportive care alone, that is usually measured in decades rather than years. 1 However, a facade of benign myeloproliferation masks a clone of transformed hematopoietic stem cells capable of expansion and transformation to an aggressive . . .

The new edition of the 2016 World Health Organization (WHO) classification system for tumors of the hematopoietic and lymphoid tissues was published in September 2017. Under the category of myeloproliferative neoplasms (MPNs), the revised document includes seven subcategories: chronic myeloid leukemia, chronic neutrophilic leukemia, polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), chronic eosinophilic leukemia-not otherwise specified and MPN, unclassifiable (MPN-U); of note, mastocytosis is no longer classified under the MPN category. In the current review, we focus on the diagnostic criteria for JAK2/CALR/MPL mutation-related MPNs: PV, ET, and PMF. In this regard, the 2016 changes were aimed at facilitating the distinction between masked PV and JAK2-mutated ET and between prefibrotic/early and overtly fibrotic PMF. In the current communication, we (i) provide practically useful resource tables and graphs on the new diagnostic criteria including outcome, (ii) elaborate on the rationale for the 2016 changes, (iii) discuss the complementary role of mutation screening, (iv) address ongoing controversies and propose solutions, (v) attend to the challenges of applying WHO criteria in routine clinical practice, and (vi) outline future directions from the perspectives of the clinical pathologist.

We report the clinical presentation and risk factors for survival in 175 patients with myeloproliferative neoplasms (MPN) and COVID-19, diagnosed between February and June 2020. After a median follow-up of 50 days, mortality was higher than in the general population and reached 48% in myelofibrosis (MF). Univariate analysis, showed a significant relationship between death and age, male gender, decreased lymphocyte counts, need for respiratory support, comorbidities and diagnosis of MF, while no association with essential thrombocythemia (ET), polycythemia vera (PV), and prefibrotic-PMF (pre-PMF) was found. Regarding MPN-directed therapy ongoing at the time of COVID-19 diagnosis, Ruxolitinib (Ruxo) was significantly more frequent in patients who died in comparison with survivors ( p  = 0.006). Conversely, multivariable analysis found no effect of Ruxo alone on mortality, but highlighted an increased risk of death in the 11 out of 45 patients who discontinued treatment. These findings were also confirmed in a propensity score matching analysis. In conclusion, we found a high risk of mortality during COVID-19 infection among MPN patients, especially in MF patients and/or discontinuing Ruxo at COVID-19 diagnosis. These findings call for deeper investigation on the role of Ruxo treatment and its interruption, in affecting mortality in MPN patients with COVID-19.

Background The Philadelphia chromosome−negative myeloproliferative neoplasms (MPN) myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) negatively affect patient quality of life (QoL) and are associated with increased risk of mortality. Methods The MPN Landmark survey was conducted from May to July 2014 in patients with MF, PV, or ET under active management in the United States. The survey assessed respondent perceptions of disease burden and treatment management and included questions on overall disease burden, QoL, activities of daily living, and work productivity. Outcomes were further analyzed by calculated (ie, not respondent-reported) prognostic risk score and symptom severity quartile. Results The survey was completed by 813 respondents (MF, n  = 207; PV, n  = 380; ET, n  = 226). The median respondent age in each of the 3 MPN subtypes ranged from 62 to 66 years; median disease duration was 4 to 7 years. Many respondents reported that they had experienced MPN-related symptoms ≥1 year before diagnosis (MF, 49 %; PV, 61 %; ET, 58 %). Respondents also reported that MPN-related symptoms reduced their QoL, including respondents with low prognostic risk scores (MF, 67 %; PV, 62 %; ET, 57 %) and low symptom severity (MF, 51 %; PV, 33 %; ET, 15 %). Many respondents, including those with a low prognostic risk score, reported that their MPN had caused them to cancel planned activities or call in sick to work at least once in the preceding 30 days (cancel planned activities: MF, 56 %; PV, 35 %; ET, 35 %; call in sick: MF, 40 %; PV, 21 %; ET, 23 %). Conclusions These findings of the MPN Landmark survey support previous research about the symptom burden experienced by patients with MPNs and are the first to detail the challenges that patients with MPNs experience related to reductions in activities of daily living and work productivity.

Constitutive JAK2 signaling is central to myeloproliferative neoplasm (MPN) pathogenesis and results in activation of STAT, PI3K/AKT, and MEK/ERK signaling. However, the therapeutic efficacy of current JAK2 inhibitors is limited. We investigated the role of MEK/ERK signaling in MPN cell survival in the setting of JAK inhibition. Type I and II JAK2 inhibition suppressed MEK/ERK activation in MPN cell lines in vitro, but not in Jak2V617F and MPLW515L mouse models in vivo. JAK2 inhibition ex vivo inhibited MEK/ERK signaling, suggesting that cell-extrinsic factors maintain ERK activation in vivo. We identified PDGFRα as an activated kinase that remains activated upon JAK2 inhibition in vivo, and PDGF-AA/PDGF-BB production persisted in the setting of JAK inhibition. PDGF-BB maintained ERK activation in the presence of ruxolitinib, consistent with its function as a ligand-induced bypass for ERK activation. Combined JAK/MEK inhibition suppressed MEK/ERK activation in Jak2V617F and MPLW515L mice with increased efficacy and reversal of fibrosis to an extent not seen with JAK inhibitors. This demonstrates that compensatory ERK activation limits the efficacy of JAK2 inhibition and dual JAK/MEK inhibition provides an opportunity for improved therapeutic efficacy in MPNs and in other malignancies driven by aberrant JAK-STAT signaling.

Chronic exposure to JAK2 inhibitors leads to reactivation of downstream signalling through the formation of heterodimers between JAK2 and other JAK kinases in myeloproliferative neoplasms, which can be overcome with Hsp90 inhibitors. Resistance to JAK2 inhibitors Mutations in JAK kinases, in particular JAK2, are frequent in some malignancies and JAK inhibitors have been trialled for example in patients with myeloproliferative neoplasms (MPNs). Here, Ross Levine and colleagues demonstrate that MPN cells can persist under conditions of chronic JAK2 inhibition, because JAK2 forms a heterodimer with other JAK kinases, leading to persistent JAK2 activation. This mode of drug 'persistence' seems to occur in patients treated with JAK2 inhibitor. Therapeutic approaches that induce JAK2 degradation may therefore be more effective than treatment with JAK2 inhibitors alone. The identification of somatic activating mutations in JAK2 (refs  1–4 ) and in the thrombopoietin receptor gene ( MPL ) 5 in most patients with myeloproliferative neoplasm (MPN) led to the clinical development of JAK2 kinase inhibitors 6 , 7 . JAK2 inhibitor therapy improves MPN-associated splenomegaly and systemic symptoms but does not significantly decrease or eliminate the MPN clone in most patients with MPN. We therefore sought to characterize mechanisms by which MPN cells persist despite chronic inhibition of JAK2. Here we show that JAK2 inhibitor persistence is associated with reactivation of JAK–STAT signalling and with heterodimerization between activated JAK2 and JAK1 or TYK2, consistent with activation of JAK2 in trans by other JAK kinases. Further, this phenomenon is reversible: JAK2 inhibitor withdrawal is associated with resensitization to JAK2 kinase inhibitors and with reversible changes in JAK2 expression. We saw increased JAK2 heterodimerization and sustained JAK2 activation in cell lines, in murine models and in patients treated with JAK2 inhibitors. RNA interference and pharmacological studies show that JAK2-inhibitor-persistent cells remain dependent on JAK2 protein expression. Consequently, therapies that result in JAK2 degradation retain efficacy in persistent cells and may provide additional benefit to patients with JAK2-dependent malignancies treated with JAK2 inhibitors.

Aspartyl-tRNA synthetase (DARS) is implicated in several cancers, but its role in BCR::ABL-negative JAK2V617F-positive myeloproliferative neoplasms (MPNs) is unclear. This study evaluated DARS expression in MPN subtypes and its associations with clinical parameters and survival. Diagnostic bone marrow biopsies from 121 JAK2V617F-positive MPN patients (PV, n = 34; ET, n = 25; PMF, n = 54; MPN-U, n = 8) were stained on a Ventana BenchMark XT immunostainer using anti-DARS antibody (ABclonal A6574). DARS immunoreactive score (IRS) was determined by multiplying intensity (0–3) and percentage of positive cells (0–4). Inter-observer agreement was excellent (κ = 0.89, 95% CI: 0.83–0.95). Patients were stratified using the cohort’s median cutoff (IRS = 9) for survival analysis. Statistical tests included Kruskal-Wallis with effect sizes and multivariate Cox regression. DARS IRS differed across subtypes (H = 14.19, p = 0.003, η²=0.10): PV median 9 with IQR (9–12), ET 9 (8–12), PMF 8 (6–9), and MPN-U 10.5 (6–12). PV vs. PMF differences: intensity p = 0.001 (r = 0.35), IRS p < 0.001 (r = 0.38). DARS IRS correlated inversely with spleen size (ρ=–0.266, p = 0.003, 95% CI: − 0.43 to − 0.09), LDH (ρ=–0.194, p = 0.033), and fibrosis grade (ρ=–0.280, p = 0.002), and positively with hemoglobin (ρ = 0.308, p = 0.001, 95% CI: 0.13–0.47). High DARS expression independently predicted improved leukemia-free survival (LFS) (HR = 0.42, p = 0.007, 95% CI: 0.22–0.80) after adjusting for age, subtype, and fibrosis. DARS is differentially expressed in MPN subtypes. Its association with enhanced LFS identifies DARS as a potential prognostic biomarker warranting validation in larger cohorts.

Purpose of Review This report summarizes key insights from the 8th Annual International Symposium on Myeloproliferative Neoplasms (MPN Asia 2025). The symposium brought together global experts to discuss advancements in MPN biology, diagnostics, and therapeutics, with a focus on emerging molecular understanding, novel treatment strategies and real-world data. Recent Findings Molecular profiling has become essential in MPN risk stratification and therapeutic decision-making. High-risk mutations (e.g., ASXL1, TP53) and inflammatory pathways (e.g., IL-17, NF-κB) were shown to correlate with disease progression and transformation. Interferon-based therapy is increasingly used in younger, low-risk, or treatment-naïve patients, and is also being investigated in myelofibrosis and essential thrombocythemia. Ropeginterferon alfa-2b, a novel interferon-based therapy, demonstrated durable clinical efficacy in polycythemia vera. Its high initial-dose and accelerated titration (HIDAT) regimen led to fast achievement of complete hematologic response, rapid reductions in JAK2 V617F allele burden, and high complete molecular response rate. Combination regimens involving ruxolitinib and agents such as pelabresib, selinexor, and interferon showed potential for enhanced efficacy. Population-based studies from Asia contributed regional epidemiological and treatment data, reinforcing the role of real-world evidence. Modern prognostic models such as MIPSS70+ v2.0 and GIPSS were discussed for more precise risk prediction. Preliminary findings also suggest ropeginterferon alfa-2b may be a safe option during pregnancy. Summary MPN Asia 2025 highlighted the growing role of molecular diagnostics and targeted therapeutics in the management of MPNs. Ropeginterferon alfa-2b has emerged as a therapeutic potential across the MPN spectrum. Its early use and personalized strategies are increasingly recognized. Real-world data and regional insights are shaping a more nuanced, globally informed approach to MPN care.

Classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are a heterogeneous group of hematopoietic malignancies including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The JAK2V617F mutation plays a central role in these disorders and can be found in 90% of PV and ~50–60% of ET and PMF. Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional regulator of the response to decreased oxygen levels. We demonstrate the impact of pharmacological inhibition and shRNA-mediated knockdown (KD) of HIF-1α in JAK2V617F-positive cells. Inhibition of HIF-1 binding to hypoxia response elements (HREs) with echinomycin, verified by ChIP, impaired growth and survival by inducing apoptosis and cell cycle arrest in Jak2V617F-positive 32D cells, but not Jak2WT controls. Echinomycin selectively abrogated clonogenic growth of JAK2V617F cells and decreased growth, survival, and colony formation of bone marrow and peripheral blood mononuclear cells and iPS cell-derived progenitor cells from JAK2V617F-positive patients, while cells from healthy donors were unaffected. We identified HIF-1 target genes involved in the Warburg effect as a possible underlying mechanism, with increased expression of Pdk1, Glut1, and others. That was underlined by transcriptome analysis of primary patient samples. Collectively, our data show that HIF-1 is a new potential therapeutic target in JAK2V617F-positive MPN.