Inflammation as a cause of acute myocardial infarction in patients with myeloproliferative neoplasm

Myeloproliferative neoplasms(MPN)are a group of diseases characterized by the clonal proliferation of hematopoietic progenitor or stem cells.They are clinically classifiable into four main diseases:chronic myeloid leukemia,essential thrombocythemia,polycythemia vera,and primary myelofibrosis.These pathologies are closely related to cardio-and cerebrovascular diseases due to the increased risk of arterial thrombosis,the most common underlying cause of acute myocardial infarction.Recent evidence shows that the classical Virchow triad(hypercoagulability,blood stasis,endothelial injury)might offer an explanation for such association.Indeed,patients with MPN might have a higher number and more reactive circulating platelets and leukocytes,a tendency toward blood stasis because of a high number of circulating red blood cells,endothelial injury or overactivation as a consequence of sustained inflammation caused by the neoplastic clonal cell.These abnormal cancer cells,especially when associated with the JAK2V617F mutation,tend to proliferate and secrete several inflammatory cytokines.This sustains a pro-inflammatory state throughout the body.The direct consequence is the induction of a pro-thrombotic state that acts as a determinant in favoring both venous and arterial thrombus formation.Clinically,MPN patients need to be carefully evaluated to be treated not only with cytoreductive treatments but also with cardiovascular protective strategies.

Budd-Chiari syndrome in myeloproliferative neoplasms:A review of literature

Myeloproliferative neoplasms(MPNs)are defined as clonal disorders of the hematopoietic stem cell in which an exaggerated production of terminally differentiated myeloid cells occurs.Classical,Philadelphia-negative MPNs,i.e.,polycythemia vera,essential thrombocythemia and primary myelofibrosis,exhibit a propensity towards the development of thrombotic complications that can occur in unusual sites,e.g.,portal,splanchnic or hepatic veins,the placenta or cerebral sinuses.The pathogenesis of thrombotic events in MPNs is complex and requires an intricate mechanism involving endothelial injury,stasis,elevated leukocyte adhesion,integrins,neutrophil extracellular traps,somatic mutations(e.g.,the V617F point mutation in the JAK2 gene),microparticles,circulating endothelial cells,and other factors,to name a few.Herein,we review the available data on Budd-Chiari syndrome in Philadelphia-negative MPNs,with a particular focus on its epidemiology,pathogenesis,histopathology,risk factors,classification,clinical presentation,diagnosis,and management.

Acute myocardial infarction in myeloproliferative neoplasms

Myeloproliferative neoplasms(MPNs)are a heterogeneous group of hematologic malignancies characterized by an abnormal proliferation of cells of the myeloid lineage.Affected individuals are at increased risk for cardiovascular and thrombotic events.Myocardial infarction(MI)may be one of the earliest clinical manifestations of MPNs or may be a thrombotic complication that develops during the natural course of the disease.In the present review,we examine the epidemiology,pathogenesis,clinical presentation,and management of MI in MPNs based on the available literature.Moreover,we review potential biomarkers that could mediate the MI-MPNs crosstalk,from classical biochemical tests,e.g.,lactate dehydrogenase,creatine kinase and troponins,to pro-inflammatory cytokines,oxidative stress markers,and clonal hematopoiesis.

Risk of hepatitis B reactivation in patients with myeloproliferative neoplasms treated with ruxolitinib

Classical Philadelphia-negative myeloproliferative neoplasms(MPNs),i.e.,polycythemia vera,essential thrombocythemia,and primary/secondary myelofibrosis,are clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells occurs.MPNs are characterized by mutations in driver genes,the JAK2V617F point mutation being the most commonly detected genetic alteration in these hematological malignancies.Thus,JAK inhibition has emerged as a potential therapeutic strategy in MPNs,with ruxolitinib being the first JAK inhibitor developed,approved,and prescribed in the management of these blood cancers.However,the use of ruxolitinib has been associated with a potential risk of infection,including opportunistic infections and reactivation of hepatitis B.Here,we briefly describe the association between ruxolitinib treatment in MPNs and hepatitis B reactivation.

Toxicity of targeted anticancer treatments on the liver in myeloproliferative neoplasms

The liver has a central role in metabolism,therefore,it is susceptible to harmful effects of ingested medications(drugs,herbs,and nutritional supplements).Druginduced liver injury(DILI)comprises a range of unexpected reactions that occur after exposure to various classes of medication.Even though most cases consist of mild,temporary elevations in liver enzyme markers,DILI can also manifest as acute liver failure in some patients and can be associated with mortality.Herein,we briefly review available data on DILI induced by targeted anticancer agents in managing classical myeloproliferative neoplasms:Chronic myeloid leukemia,polycythemia vera,essential thrombocythemia,and myelofibrosis.

Exploring the mechanism of action of DHI on myeloproliferative neoplasms based on network pharmacology

Objective:The aim of this study is to explore the active ingredients and mechanism of action of danhong injection(DHI)in treating myeloproliferative neoplasms using network pharmacology.Methods:The TCMSP platform and relevant literature were used to search for the active ingredients and targets of Radix Salviae and Carthami Flos in DHI.Disease targets related to myeloproliferative neoplasms were obtained from the GEO database,GeneCards,and DisGeNET database.The queried component targets were normalized using the UniProt database.Potential targets were identified by constructing protein-protein interactions networks using STRING 11.5 and visualized and analyzed using Cytoscape 3.9.1.GO and KEGG analysis were performed using the Metascape platform,and visualization was done using the built-in plug-in CluoGO or SangerBox platforms with Cytoscape 3.9.1.Results:The active ingredients of DHI for treating myeloproliferative neoplasms mainly consist of flavonoids and o-benzoquinones,including quercetin,luteolin,kaempferol,stigmasterol,tanshinone iia,cryptotanshinone,beta-carotene,2-isopropyl-8-methylphenanthrene-3,4-dione,and neocryptotanshinone ii.The potential targets are JUN,TP53,STAT3,AKT1,MAPK1,RELA,TNF,MAPK14,IL6,and FOS.The relevant signaling pathways involved are mainly TNFαsignaling pathway,PI3K-Akt signaling pathway,apoptosis,IL-17 signaling pathway,cellular senescence,MAPK signaling pathway,p53 signaling pathway,JAK-STAT signaling pathway,and NF-kappa B signaling.Conclusions:DHI acts mainly through flavonoids and o-benzoquinones to treat myeloproliferative neoplasms in a multi-targeted and multi-pathway manner.

Clinical management of myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes

The myelodysplastic/myeloproliferative neoplasms(MDS/MPNs) are a unique group of hematologic malignancies characterized by concomitant myelodysplastic and myeloproliferative features. According to the 2008 WHO classification, the category includes atypical chronic myeloid leukemia(a CML), chronic myelomonocytic leukemia(CMML), juvenile myelomonocytic leukemia(JMML), MDS/MPN-unclassifiable(MDS/MPN-U), and the provisional entity refractory anemia with ring sideroblasts and thrombocytosis(RARS-T). Although diagnosis currently remains based on clinicopathologic features, the incorporation of nextgeneration platforms has allowed for the recent molecular characterization of these diseases which has revealed unique and complex mutational profiles that support their distinct biology and is anticipated to soon play an integral role in diagnosis,prognostication, and treatment. Future goals of research should include the development of disease-modifying therapies, and further genetic understanding of the category will likely form the foundation of these efforts.

European vs 2015-World Health Organization clinical molecular and pathological classification of myeloproliferative neoplasms

The BCR/ABL fusion gene or the Ph^1-chromosome in the t(9;22)(q34;q11)exerts a high tyrokinase acticity,which is the cause of chronic myeloid leukemia(CML).The1990 Hannover Bone Marrow Classification separated CML from the myeloproliferative disorders essential thrombocythemia(ET),polycythemia vera(PV)and chronic megakaryocytic granulocytic myeloproliferation(CMGM).The 2006-2008 European Clinical Molecular and Pathological(ECMP)criteria discovered 3variants of thrombocythemia:ET with features of PV(prodromal PV),"true"ET and ET associated with CMGM.The 2008 World Health Organization(WHO)-ECMP and 2014 WHO-CMP classifications defined three phenotypes of JAK2^(V617F)mutated ET:normocellular ET(WHO-ET),hypercelluar ET due to increased erythropoiesis(prodromal PV)and ET with hypercellular megakaryocytic-granulocytic myeloproliferation.The JAK2^(V617F)mutation load in heterozygous WHO-ET is low and associated with normal life expectance.The hetero/homozygous JAK2^(V617F)mutation load in PV and myelofibrosis is related to myeloproliferative neoplasm(MPN)disease burden in terms of symptomaticsplenomegaly,constitutional symptoms,bone marrow hypercellularity and myelofibrosis.JAK2 exon 12mutated MPN presents as idiopathic eryhrocythemia and early stage PV.According to 2014 WHO-CMP criteria JAK2 wild type MPL^(515)mutated ET is the second distinct thrombocythemia featured by clustered giant megakaryocytes with hyperlobulated stag-horn-like nuclei,in a normocellular bone marrow consistent with the diagnosis of"true"ET.JAK2/MPL wild type,calreticulin mutated hypercellular ET appears to be the third distinct thrombocythemia characterized by clustered larged immature dysmorphic megakaryocytes and bulky(bulbous)hyperchromatic nuclei consistent with CMGM or primary megakaryocytic granulocytic myeloproliferation.

PVSG and WHO vs European Clinical,Molecular and Pathological Criteria for prefibrotic myeloproliferative neoplasms

The Polycythemia Vera Study Group(PVSG),World Health Organization(WHO) and European Clinical,Molecular and Pathological(ECMP) classifications agree upon the diagnostic criteria for polycythemia vera(PV) and advanced primary myelofibrosis(MF). Essential thrombocythemia(ET) according to PVSG and 2007/2008 WHO criteria comprises three variants of JAK2V617 F mutated ET when the ECMP criteria are applied. These include normocellular ET,hypercellular ET with features of early PV(prodromal PV),and hypercellular ET due to megakaryocytic,granulocytic myeloprolifera-tion(ET.MGM). Evolution of prodromal PV into overt PV is common. Development of MF is rare in normocellular ET(WHO-ET) but rather common in hypercellular ET.MGM. The JAK2V617 F mutation burden in heterozygous mutated normocellular ET and in heterozygous/homozygous or homozygous mutated PV and ET.MGM is of major prognostic significance. JAK2/MPL wild type ET associated with prefibrotic primary megakaryocytic and granulocytic myeloproliferation(PMGM) is characterized by densely clustered immature dysmorphic megakaryocytes with bulky(bulbous) hyperchromatic nuclei,which are never seen in JAK2V617 F mutated ET,and PV and also not in MPL515 mutated normocellular ET(WHO-ET). JAK2V617 mutation burden,spleen size,LDH,circulating CD34+ cells,and pre-treatment bone marrow histopathology are mandatory to stage the myeloproliferative neoplasms ET,PV,PMGM for proper prognosis assessment and therapeutic implications. MF itself is not a disease because reticulin fibrosis and reticulin/collagen fibrosis are secondary responses of activated polyclonal fibroblasts to cytokines released from the clonal myeloproliferative granulocytic and megakaryocytic progenitor cells in ET.MGM,PV and PMGM.

The JAK2^V617FMutation Seen in Myeloproliferative Neoplasms (MPNs) Occurs in Patients with Inflammatory Bowel Disease: Implications of a Pilot Study

Patients with IBD frequently have hematologic abnormalities suggestive of JAK2 mutated MPNs, but are traditionally classified as reactive processes. Haplotype 46/1 is a well-characterized genetic predisposition, common to both inflammatory bowel disease (IBD) and myeloproliferative neoplasms (MPN). In view of this shared genetic predisposition, we measured the frequency of the JAK2V617F mutation in IBD patients with thrombocytosis or erythrocytosis, in order to ascertain whether a higher than expected proportion of these patients may in fact have underlying MPNs. 1121 patients were identified with an active diagnosis of Crohn’s disease or ulcerative colitis, of which 474 had either thrombocytosis or erythrocytosis. Patients with abnormal counts were tested for the JAK2V617F mutation during routine follow-up visits. Interim analysis of first 23 patients tested was performed to assess whether the JAK2V617F positivity rate was statistically significant compared with known expected frequencies in a comparable control population. Of 23 patients, 13 patients had thrombocytosis and 10 had erythrocytosis. Three patients with thrombocytosis (23%), and 1 patient with erythrocytosis (10%), tested positive for JAK2V617F, exceeding the expected thresholds for statistical significance. In patients with IBD and thrombocytosis or erythrocytosis, a meaningful proportion may harbor an undiagnosed MPN, as indicated by clonal abnormalities such as JAK2V617F. These findings imply the need for increased testing of these patients for clonal hematologic abnormalities, and importantly, if found, suggest the need for therapeutic strategies with drugs, such as JAK2 inhibitors, in patients with both MPN and IBD.

Identification of <i>JAK2</i>(V617F) Mutation in Myeloproliferative Neoplasms by Using Allele Specific Polymerase Chain Reaction (AS-PCR)

Myeloproliferative neoplasms (MPNs) are a group of clonal haematopoietic stem cell disorders characterized by the proliferation of one or more myeloid cell lineages. According to WHO classification, the Janus associated kinase 2 (JAK2) V617F mutation is one of the major diagnostic criteria in BCR-ABL1 negative myeloproliferative neoplasms. The aim of this study is to detect the JAK2 (V617F) mutation in patients with myeloproliferative neoplasms to get accurate diagnosis and proper management. A total of 90 clinically diagnosed MPN patients attending to Department of Clinical Haematology, Yangon General Hospital were enrolled in this study. The mean age was 53.4 ± 14 years which ranged from 16 to 81 years old and male and female ratio was 2.4:1. The identification of JAK2 (V617F) point mutation was found to be positive in 44/90 MPN patients (48.9%). According to MPN subtypes, the JAK2 mutation positivity was found in 19 out of 46 polycythemia vera patients (41.3%), 17 out of 25 essential thrombocythemia patients (68%), 8 out of 15 primary myelofibrosis patients (53.3%), 0 of 4 others myeloproliferative neoplasms (0%). Confirmation of each of nine JAK2 mutation positive and negative samples was done by Sanger sequencing. The arterial or venous thrombotic attack was found in 32/44 JAK2 mutation positive cases (72.7%) and 12/44 JAK2 mutation negative cases (27.3%). The association between thrombotic attack and presence of JAK2 mutation was statistically significance with p = 0.000. The diagnosis of myeloproliferative neoplasms mainly relies on the molecular genetics according to WHO classification. The Allele specific PCR reaction is sensitive, simple test and relatively cost-effective. Therefore, the identification of JAK2 (V617F) somatic point mutation by AS-PCR should be implemented as a routine diagnosis procedure for patients with chronic and suspected myeloproliferative neoplasms.

Myeloproliferative neoplasms complicated withβ-thalassemia:Two case report

BACKGROUND BCR-ABL-negative myeloproliferative neoplasms(MPNs)are clonal hematopoietic stem cell disorders characterized by the proliferation of one or more myeloid lineages and by mutually exclusive JAK2 V617F,CALR,and MPL[A1]mutations.The combination of MPN and thalassemia is extremely unusual.Several cases with myeloproliferative neoplasms andβ-thalassemia have been reported.However,these have not been extensively reviewed.The present report describes two cases of myeloproliferative neoplasms complicated withβ-thalassemia and reviews all similar cases reported in the literature.CASE SUMMARY We report two patients who were diagnosed with myeloproliferative neoplasms complicated withβ-thalassemia.Both patients had abnormal increases in platelet counts.Based on bone marrow pathology and molecular biology assessment,we made the diagnosis of myeloproliferative neoplasms complicated withβ-thalassemia.The female patient was given hydroxyurea and interferon,which enabled good control of her blood counts;the male patient was given ruxolitinib tablets,thalidomide tablets,and interferon to control the condition,but the patient poorly responded to drug treatment and died of gastrointestinal bleeding six months later.CONCLUSION Given the findings of our cases and the literature review,we hypothesize that myeloproliferative neoplasms complicated withβ-thalassemia can lead to rapid disease progression and a poor prognosis.

Incidence in Ph-Negative Myeloproliferative Neoplasms in Armenia from 2005 to 2019

Introduction: Enhancements of laboratory diagnostics and the emergence of new therapies had a significant impact on the incidence, prevalence and survival of patients with myeloproliferative neoplasms (MPN). Published epidemiology data are scarce, and multiple sources are needed to assess the disease burden. The aim of our work was to identify the patterns and trends of incidence, prevalence and survival of patients with MPN in the Republic of Armenia (RA) for the period 2005-2019. Methods: The data from Hematology Center blood diseases register, Oncological Center cancer register, as well as the data from death registration were the basis of our research. Demographic data were obtained from National Statistical Office of RA. Results: Analysis of the data obtained has shown that during the reporting period the average annual incidence of MPN was 1.84 per 100.000 inhabitants, including 2.1 for males and 1.64 for females. Analysis of incidence rates of MPN in relation to sex and age in the period under study revealed high rates in patients in groups 65 - 74 (8.3) and 55 - 64 (5.12 per 100 thousand years), respectively. According to the data obtained in the group of patients with MPN, the high annual average incidence rates are noted in primary myelofibrosis (PMF) (1.09 in 2018) and polycythemia vera (PV) (0.89 in 2016), the lowest for essential thrombocythemia (ET) (0.7 in 2016) per 100.000 population, respectively. In comparing our data to those obtained for 1966-1971 and 1998-2004 periods, one may detect a statistically significant increase in the total incidence of PMF and PV (p < 0.001). Conclusions: Analysis of the incidence rate in MPNs adjusted for age and gender shown the prevalence in group 65 - 74 (8.3) and in group 55 - 64 (5.13) per 100,000 inhabitants. The peak of incidence rate for both males and females was the age 65 - 74 and the male female incidence ratio in this age group was 11.3:6.2. The increasing incidence rate in MPNs in Armenia depends on the improvement of laboratory diagnosis. Thrombotic complications are observed in patients with an MPN in 45.3% of cases. In most cases, thrombosis is the first clinical symptom of an MPN, which determines the need for the introduction into clinical practice of molecular genetic testing methods among patients with thrombosis, an increase in blood levels, splenomegaly for the early diagnosis of clonal hematopoiesis and the use of a targeted drug.

Network pharmacology prediction and molecular docking-based strategy to investigate the possibility of CPL against myeloproliferative neoplasms

Background:Compound cortex phellodendri liquid(CPL)is a kind of classical compound preparation,which has potential curative effect in treating inflammatory diseases.Increasing evidences support that inflammation plays important roles in the pathogenesis of myeloproliferative neoplasms(MPN).This study aims to preliminarily clarify the therapeutic potential and molecular mechanisms of CPL for MPN based on network pharmacology and molecular docking techniques.Methods:The active components and corresponding action targets of CPL were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),while MPN-related targets were searched through GeneCards,DisGeNET,OMIM,DrugBank and TTD databases respectively.Protein-Protein Interaction(PPI)Networks of potential targets were constructed using STRING 11.5 and analyzed visually with Cytoscape 3.9.1.In addition,Metascape platform was used for GO and KEGG analysis that were subsequently visualized with Cytoscape 3.9.1 built-in plug-ins CluoGO or SangerBox platform.Finally,Autodock Vina was used for molecular docking of potential targets and main active ingredients,which were visualized with Pymol software.Experimentally,we used in vitro mouse primary cells culture system to evaluate the effect of CPL on the erythroid and megakaryocytes differentiation that are excessively driven in MPN respectively.Results:The active components of CPL in the treatment of MPN are mainly flavonoids.The core proteins of CPL for MPN intervention are correlated to TP53,AKT1,JUN,CASP3,EGFR,TNF,MYC,IL6.Multiple signaling pathways were closely related to the treatment of MPN intervened by CPL,including PI3K-Akt signaling,TNF-αsignaling,JAK-STAT signaling and NF-κB signaling pathways.These potential targets had good conformation with the core active ingredients of CPL.In line with above findings,we demonstrated that CPL significantly inhibits the proliferation of differentiation of erythrocytes and megakaryocytes in vitro,further supporting the therapeutic potential of CPL for MPN.Conclusion:This study revealed the active ingredients and potential molecular mechanism of CPL in the treatment of MPN,providing a reference for subsequent basic research.

Myeloproliferative and thrombotic burden and treatment outcome of thrombocythemia and polycythemia patients

Prospective studies indicate that the risk of microvascular and major thrombosis in untreated thrombocythemia in various myeloproliferative neoplasms(MPN-T) is not age dependent and causally related to platelet-mediated thrombosis in early, intermediate and advanced stages of thrombocythemia in MPN-T. If left untreated both microvascular and major thrombosis frequently do occur in MPN-T, but can easily be cured and prevented by low dose aspirin as platelet counts are above 350 × 109/L. The thrombotic risk stratification in the retrospective Bergamo study has been performed in 100 essential thrombocythemia(ET) patients not treated with aspirin thereby overlooking the discovery in 1985 of aspirin responsive platelet-mediated arteriolar and arterial thrombotic tendency in MPN-T disease of ET and polycythemia vera(PV) patients. The Bergamo definition of high thrombotic risk and its persistence in the 2012 International Prognostic Score for ET is based on statistic mystification and not applicable for low and intermediate MPN-T disease burden in ET and PV patients on aspirin. With the advent of molecular screening of MPN patients, MPN-T disease associated with significant leukocytosis, thrombocytosis, constitutional symptoms and/or moderate splenomegaly are candidates for low dose peglyated interferon(Pegasys R, 45 mg/m L once per week or every two weeks) as the first line myeloreductive treatment option in JAK2V617 F mutated MPN-T disease in ET and PV patients. If non-responsive to or side effects induced by IFN, hydroxyurea is the second line myelosuppressive treatment option in JAK2V617 F mutated ET and PV patients with increased MPN-T disease burden.

Therapy-related myeloid neoplasms - what have we learned so far?

Therapy-related myeloid neoplasms are neoplastic processes arising as a result of chemotherapy, radiation therapy, or a combination of these modalities given for a primary condition. The disease biology varies based on the etiology and treatment modalities patients receive for their primary condition. Topoisomerase II inhibitor therapy results in balanced translocations. Alkylating agents, characteristically, give rise to more complex karyotypes and mutations in p53. Other etiologies include radiation therapy, high-dose chemotherapy with autologous stem cell transplantation and telomere dysfunction. Poor-risk cytogenetic abnormalities are more prevalent than they are in de novo leukemias and the prognosis of these patients is uniformly dismal. Outcome varies according to cytogenetic risk group. Treatment recommendations should be based on performance status and karyotype. An in-depth understanding of risk factors that lead to the development of therapy-related myeloid neoplasms would help developing risk-adapted treatment protocols and monitoring patients after treatment for the primary condition, translating into reduced incidence, early detection and timely treatment.

Micheliolide exerts effects in myeloproliferative neoplasms through inhibiting STAT3/5 phosphorylation via covalent binding to STAT3/5 proteins

Ruxolitinib is a cornerstone of management for some subsets of myeloproliferative neoplasms(MPNs);however,a considerable number of patients respond suboptimally.Here,we evaluated the efficacy of micheliolide(MCL),a natural guaianolide sesquiterpene lactone,alone or in combination with ruxolitinib in samples from patients with MPNs,JAK2V617F-mutated MPN cell lines,and a Jak2V617F knock-in mouse model.MCL effectively suppressed colony formation of hematopoietic progenitors in samples from patients with MPNs and inhibited cell growth and survival of MPN cell lines in vitro.Co-treatment with MCL and ruxolitinib resulted in greater inhibitory effects compared with treatment with ruxolitinib alone.Moreover,dimethylaminomicheliolide(DMAMCL),an orally available derivative of MCL,significantly increased the efficacy of ruxolitinib in reducing splenomegaly and cytokine production in Jak2V617F knock-in mice without evident effects on normal hematopoiesis.Importantly,MCL could target the Jak2V617F clone and reduce mutant allele burden in vivo.Mechanistically,MCL can form a stable covalent bond with cysteine residues of STAT3/5 to suppress their phosphorylation,thus inhibiting JAK/STAT signaling.Overall,these findings suggest that MCL is a promising drug in combination with ruxolitinib in the setting of suboptimal response to ruxolitinib.

CHIP相关基因与MPN患者心脑血管事件的风险分析

目的:分析骨髓增殖性肿瘤(MPN)患者不确定潜能的克隆性造血(CHIP)相关基因突变谱和临床特征,探讨CHIP相关基因与其心脑血管事件(CCE)的相关性及可能作用机制。方法:回顾性分析2019年8月-2022年7月首都医科大学附属北京安贞医院血液科收治的73例MPN患者的临床资料和二代测序结果,采用Logistic回归分析CHIP相关基因、炎症细胞因子对MPN患者CCE的影响。结果:55例(75.3%)MPN患者检出CHIP相关基因,原发性血小板增多症(ET)和真性红细胞增多症(PV)患者CHIP相关基因各突变频率差异无统计学意义。CHIP相关基因突变以单基因形式为主,检出率从高至低依次为JAK2V617F(63.0%,46/73)、ASXL1(16.4%,12/73)、TET2(11.0%,8/73)、DNMT3A(9.6%,7/73)、SRSF2(6.9%,5/73)、SF3B1(4.1%,3/73)、TP53(1.4%,1/73)和PPMID(1.4%,1/73)。年龄>60岁患者CHIP相关基因检出率明显高于≤60岁者[91.7%(33/36)vs 59.5%(22/37)]。27例(37.0%)MPN患者伴CCE(MPN/CCE),2次CCE者5例,均为动脉事件。CCE组患者年龄(62.8±12.8 vs 53.9±15.8岁,P=0.015)、IL-1β水平(17.7±26.0vs 4.3±8.6,P=0.012)、IL-8水平(360.7±598.6 vs 108.3±317.0,P=0.045)、血栓形成史(29.6%vs 2.2%,P=0.020)和CHIP相关基因检出率(88.9%vs 67.4%,P=0.040)高于无CCE组。多因素Logistic回归分析结果显示,年龄(OR=0.917,95%CI:0.843-0.999,P=0.047)、血栓形成史(OR=34.148,95%CI:2.392-487.535,P=0.009)、任何1个CHIP相关基因突变(OR=16.065,95%CI:1.217-212.024,P=0.035)和IL-1β水平升高(OR=0.929,95%CI:0.870-0.992,P=0.027)均是MPN/CCE的独立危险因素;CHIP相关单基因突变与MPN/CCE无关,但DNMT3A(OR=88.717,95%CI:2.690-292.482,P=0.012)、ASXL1(OR=7.941,95%CI:1.045-60.353,P=0.045)突变是PV/CCE的独立危险因素。结论:MPN患者CHIP相关基因突变率高,尤其是60岁以上患者;高龄、血栓形成史、CHIP相关基因突变和IL-1β水平升高是MPN发生CCE的独立危险因素。DNMT3A、ASXL1单基因突变是PV患者CCE的独立危险因素。CHIP相关基因突变及炎症细胞因子IL-1β升高是MPN新的CCE危险因素。

BCR-ABL阴性MPN患者JAK2 V617F基因突变及其与疾病类型、血管性疾病的关系

目的 研究断裂点簇集区/Abelson白血病病毒(BCR-ABL)阴性骨髓增殖性肿瘤(MPN)患者Janus激酶2(JAK2)V617F基因突变情况及其与疾病类型、血管性疾病的关系。方法 选取2020年5月至2023年5月濮阳市安阳地区医院收治的79例BCR-ABL阴性MPN患者为研究对象,另选取同期健康体检人群80例为对照组,于入院第1天采集外周血检测血常规和凝血功能,采用荧光定量聚合酶链反应技术(PCR)技术检测JAK2 V617F基因突变率和突变负荷,根据疾病类型和是否合并血管性疾病将患者分组并比较各组检测结果,采用多因素logistic回归分析研究血管性疾病影响因素。结果 MPN组JAK2 V617F基因突变率高于对照组(P<0.05);真性红细胞增多症(PV)组、原发血小板增多症(ET)组和原发性骨髓纤维化(PMF)组JAK2 V617F突变率分别为92.31%、57.78%和62.50%,ET组和PMF组突变率均低于PV组(P<0.05),3组突变负荷差异无统计学意义(P>0.05);血管性疾病组JAK2 V617F基因突变率和突变负荷均高于非血管性疾病组(P<0.05);血管性疾病组年龄、骨髓增殖性肿瘤总症状评估问卷(MPN-10)评分、纤维蛋白原(Fib)和D-二聚体(D-D)水平高于非血管性疾病组(P<0.05),两组性别、疾病分类、血红蛋白(Hb)、白细胞(WBC)、血小板(PLT)、活化部分凝血激酶时间(APTT)和斑块厚度(PT)差异无统计学意义(P>0.05)。JAK2 V617F基因突变阳性组Fib和D-D水平均高于JAK2 V617F基因突变阴性组(P<0.05);MPN并发血管性疾病危险因素包括年龄、D-D、JAK2 V617F突变阳性和JAK2 V617F突变负荷(P<0.05)。结论 BCR-ABL阴性MPN患者JAK2 V617F基因突变率较高,且JAK2 V617F基因突变可能引起凝血异常,与疾病类型和血管性疾病均存在密切联系。

骨髓增殖性肿瘤临床病理学特征分析

目的探讨骨髓增殖性肿瘤的骨髓病理组织形态学特点,探讨其临床诊断价值。方法选取2020年1月至2023年3月本院收治的MPN患者138例,对骨髓活检组织作组织学观察及免疫组化行表型分析,同时进行基因学检测。结果138例确诊MPN患者中,BCR ABL阳性CML 39例,BCR ABL阴性MPNs中PV 13例、ET 72例和PMF 11例。经典型MPN骨髓活检组织各具有诊断性形态学特点。CML粒红系比例明显增大伴粒系核右移,巨核细胞均为胞体小、分叶少的巨核细胞,PV粒红系比例明显减小,巨核细胞形态多样,混杂分布;ET粒红系比例大致正常,巨核细胞则为胞体大、分叶多的巨核细胞;PMF巨核细胞形态怪异,核染色质深染浓集,多伴网状纤维显著性增生。结论骨髓活检组织形态在MPN精准诊断和分型中具有重要临床意义。