Predictors of survival in refractory anemia with ring sideroblasts and thrombocytosis (RARS‐T) and the role of next‐generation sequencing

Refractory anemia with ring sideroblasts and thrombocytosis (RARS‐T) shares overlapping features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). RARS‐T is characterized by SF3B1 and JAK2 mutations and prognosis is considered to be better than MDS but not as good as MPN. The objective of the study was to identify predictors of survival in RARS‐T. We analyzed clinical and laboratory variables in 82 patients and applied a 27‐gene NGS assay to 48 marrow samples obtained at diagnosis. 94% of patients had ≥1 mutations; common mutations being: SF3B1 85%, JAK2V617F 33%, ASXL1 29%, DNMT3A 13%, SETBP1 13% and TET2 10%. In a multivariable survival analysis (n = 82), anemia (P = 0.02) [HB< 10 gm/dl: HR 2.3, 95% CI 1.2–4.6] and abnormal karyotype (P =.01) [HR 6.1, 95% CI 2.7‐13.8] were independently prognostic for inferior survival. In patients with NGS information (n = 48), univariate analysis showed association between poor survival and presence of SETBP1 (P = 0.04) or ASXL1 (P = 0.08) mutations whereas the absence of these mutations (ASXL1wt/SETBP1wt) was favorable (P = 0.04); the number of concurrent mutations did not provide additional prognostication (P = 0.3). We developed a HR‐weighted prognostic model, with 2 points for an abnormal karyotype, 1 point for either ASXL1 and/or SETBP1 mutations, and 1 point for a HB level < 10 gm/dl, which effectively stratified patients into three risk categories; low (0 points), intermediate (1 point) and high (≥2 points), with median survivals of 80, 42 and 11 months respectively (P = 0.01). In summary, we confirm the unique mutational landscape in RARS‐T and provide a novel mutation‐enhanced prognostic model. Am. J. Hematol. 91:492–498, 2016. © 2016 Wiley Periodicals, Inc.     

Prevalence of overt myeloproliferative neoplasms and JAK2 V617F mutation in Korean patients with splanchnic vein thrombosis

Introduction: Myeloproliferative neoplasm (MPN) is known to be a major risk factor of splanchnic vein thrombosis (SVT). Recent studies revealed that a significant proportion of patients with SVT harbor a gain‐of‐function mutation in the JAK2 gene (V617F) with or without MPN. In this study, the authors investigated the prevalence of MPN and JAK2 V617F mutation in Korean patients with SVT. Methods: The study subjects were 26 patients diagnosed as having SVT based on Doppler ultrasound and/or computed tomography from January 2008 to January 2010 (16 men and 10 women; mean age 44 years, range 15–75 years). The clinical and laboratory data were reviewed. The JAK2 V617F mutation was detected by allele‐specific polymerase chain reaction and direct sequencing analyses using DNA from peripheral blood leukocytes. Results: Among 26 study patients, 12 had portal vein thrombosis, five had hepatic vein thrombosis, three had mesenteric, and two had splenic vein thrombosis. Four patients had thrombosis involving more than one splanchnic vein. Two patients (7.7%; 2/26) had overt MPN (essential thrombocythemia). JAK2 V617F was detected in three patients (11.5%) including the two patients with overt MPN. Thus, the prevalence of the JAK2 V617F mutation in patients with SVT but without overt MPN was 4.2% (1/24). Conclusion: The prevalence of overt MPN and that of JAK2 V617F were lower in Korean patients with SVT than in previous reports. Data from a larger number of patients with long‐term follow‐up are needed to reveal the clinical relevancy of JAK2 V617F in Korean patients with SVT.     

Prognostic irrelevance of ring sideroblast percentage in World Health Organization-defined myelodysplastic syndromes without excess blasts

The presence of ≥ 15% bone marrow (BM) ring sideroblasts (RS) and < 5% blasts is required for a diagnosis of refractory anemia with ring sideroblasts. We examined the phenotypic and prognostic relevance of this "15%" RS threshold in 200 patients with myelodysplastic syndromes (MDS) without excess blasts and with ≥ 1% RS. The impact of RS% was assessed both as a continuous and categorical variable: < 5% (n = 56), 5%-14% (n = 32), 15%-50% (n = 79), and > 50% (n = 33). RS% correlated (P < .05) directly with age, platelet count, transfusion dependency, BM cellularity, and mutant SF3B1 and inversely with hemoglobin level, multilineage dysplasia, and high-risk karyotype; but did not correlate with IDH mutations. At a median follow-up of 33 months, 156 (73%) deaths and 24 (12%) leukemic transformations were documented. Neither univariate nor multivariable analysis showed significant effect for RS% on overall or leukemia-free survival, suggesting the limited prognostic value of quantifying BM RS in MDS.     

Hemochromatosis-associated gene mutations in patients with myelodysplastic syndromes with refractory anemia with ringed sideroblasts

We observed increased ferritin levels in newly diagnosed MDS-RARS patients without transfusional iron-overload. Hence, we hypothesized RARS patients may harbor hemochromatosis-related mutations, which could contribute to the pathophysiology of this myelodysplastic syndromes (MDS) subset. We studied a cohort of 140 MDS patients: 42 with RARS, 10 with increased ringed sideroblasts, and 96 with other forms of MDS (43 RA, 27 RAEB, 17 RAEB-T, 8 MDS/MPD, 1 CMML). Patients were genotyped using restriction fragment length polymorphism, designed to detect C282Y and H63D mutations of the HFE gene. We found significantly higher frequency of heterozygosity for C282Y mutation in RARS patients compared with a large control population of matched race individuals (21 vs. 9.8% in controls, P = 0.03); H63D genotype was not significantly increased. Frequency of HFE variation in other MDS subtypes failed to differ significantly from controls. Within this group, we included patients with a rare form of MDS, provisionally subclassified by WHO as RARS with thrombocytosis (RARSt). 10/14 RARSt patients were carriers of either C282Y or H63D allele significantly increased compared with the combined prevalence in a healthy population (71 vs. 33%, P < 0.01). We found expected distribution of mutant HFE alleles in patients with other forms of MDS (9.1 vs. 9.8%, P = 0.82). Increased prevalence of HFE gene mutations is not a generalized feature of MDS, but some subgroups of MDS, especially those characterized by excessive accumulation of ringed sideroblasts, exhibit C282Y mutations at a higher frequency than in other forms of MDS and healthy controls.     

Chromosome 9p24 abnormalities: prevalence,description of novel JAK2 translocations,JAK2V617F mutation analysis and clinicopathologic correlates

Objectives: Current information is insufficient regarding the prevalence, cytogenetic details, JAK2 involvement, JAK2V617F mutational status, and clinicopathologic correlates of chromosome 9p24 abnormalities. The current study was designed to provide additional data in this regard. Methods: The Mayo Clinic cytogenetics database spanning the years 1989–2008 was screened for chromosome 9p24 abnormalities. Bone marrow (BM) morphology was re‐reviewed and relevant clinical information retrospectively obtained. Structural abnormalities of JAK2 were examined by FISH and JAK2V617F mutation analysis. Results: Among 24 262 unique patient cytogenetic studies, chromosome 9p24 abnormalities were identified in 25 patients (～0.06%): 12 with myeloid and 13 with lymphoid neoplasms. The associated karyotype was complex in 12 of the 13 lymphoid but in only four of the 12 myeloid cases. Archived BM was available in 23 cases that allowed additional FISH studies and JAK2V617F mutation analysis. FISH analysis disclosed JAK2 involvement in 10 patients including five myeloid and five lymphoid cases; the associated karyotype was complex in all the lymphoid but in none of the myeloid cases. Five patients displayed previously undescribed JAK2 translocations: t(8;9)(q22;p24), t(9;17)(p24;q23), t(4;9)(q25;p24), t(2;9)(p21;p24) and t(8;9)(q13;p24). JAK2‐associated chromosomal translocations, in a non‐complex karyotype setting, were documented in four patients, all of whom carried a diagnosis of myeloproliferative neoplasms (MPN) and harbored JAK2V617F. Two patients with diffuse large B cell lymphoma displayed complex karyotype and JAK2 amplification by FISH. Conclusions: Chromosome 9p24 abnormalities are rare and do not always involve JAK2. The subset with JAK2 translocations are usually associated with MPN and harbor JAK2V617F, suggesting a cause‐effect relationship. The current study also describes five novel translocations involving JAK2.     

Risk models predicting survival after reduced‐intensity transplantation for myelofibrosis

To define a prognostic model for predicting outcome of reduced‐intensity allogeneic stem cell transplantation (RIC‐ASCT) for myelofibrosis we evaluated 150 homogenously treated patients and developed a new risk score for overall survival (OS). In a multivariate Cox model for OS, only JAK2 V617F wild‐type, age ≥57 years and constitutional symptoms were independently predictive for OS (Hazard Ratio: 2·02; 2·43 and 2·80 respectively). Depending on the presence of one, two or all of these factors, HR of death was 3·08; 4·70 and 16·61 respectively (P < 0·001). This score was compared to the Lille, Cervantes, International Prognostic Scoring System (IPSS), dynamic IPSS (DIPSS) and modified European Blood and Marrow Transplantation Group (EBMT) scores. Lille score correlated significantly with OS but discriminated poorly between the intermediate and high‐risk groups (5‐year OS 56% and 51% respectively). IPSS and DIPSS correlated significantly with OS but differences between intermediate‐1 and intermediate‐2 groups were not significant (5‐year OS 78% vs. 78% and 70%, 60% respectively). Modified EBMT and Cervantes models did not predict OS post‐ASCT. In conclusion, a simple model which includes: age, JAK2 V617F‐status and constitutional symptoms can clearly separate distinct risk groups and can be used in addition to the Lille model to predict OS after RIC‐ASCT for myelofibrosis.     

Occurrence of the JAK2 V617F mutation in the WHO provisional entity: myelodysplastic/myeloproliferative disease, unclassifiable-refractory anemia with ringed sideroblasts associated with marked thrombocytosis

The JAK2/V617F mutation has been noted in essential thrombocytemia. We investigated 19 cases with refractory anemia with ringed sideroblasts (RARS), including three RARS with thrombocytosis (RARS-T). Only the RARS-T patients showed this mutation. More cases need to be analyzed to determine the prevalence of the JAK2/V617F mutation in RARS-T.     

Evaluation of the prevalence and prospective clinical impact of the JAK2 V617F mutation in coronary patients

The JAK2 V617F mutation is not only found in the majority of patients with myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), but also has been reported in individuals without overt MPN. A close relation of the JAK2 V617F mutation to atherothrombotic events has been described, at least in patients with MPN. The prevalence of the JAK2 V617F mutation and its clinical impact in coronary patients is unknown. To address this issue, DNA samples from 1,589 subjects undergoing coronary angiography with up to 11 years of follow up were genotyped using allele‐specific real‐time PCR assays. Prevalence of the JAK2 V617F mutation was 1.32% (n = 21) in coronary patients. Two JAK2 V617F positive patients showed baseline platelet counts indicative for ET and a third patient developed ET during follow up, finally resulting in a percentage of 0.188% of ET cases. This corresponds to an up to fivefold accumulation of ET cases in coronary patients compared with the general population. Our study showed no impact of the JAK2 V617F mutation on future atherothrombotic events or overall survival (HR = 1.04 [0.33–3.27]; P = 0.949 and HR = 0.35 [0.05–2.46]; P = 0.288, respectively). Therefore, our data suggest that JAK2 V617F positive coronary patients are not at increased risk for future atherothrombotic complications. Routine mutation screening in coronary patients is, therefore, not warranted. However, number of ET cases appears to be accumulated in coronary patients. For this reason, we recommend JAK2 V617F testing only in coronary patients showing abnormal blood cell counts for further clarification. Am. J. Hematol. 89:295–301, 2014. © 2013 Wiley Periodicals, Inc.     

Refractory anemia with ringed sideroblasts associated with thrombocytosis: comparative analysis of marked with non-marked thrombocytosis, and relationship with JAK2 V617F mutational status

The World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues (2001) defined a provisional entity named refractory anemia with ringed sideroblasts associated to marked thrombocytosis (RARS-MT). Diagnosis of RARS-MT requires more than 15% of ringed sideroblasts in bone marrow aspirate and the existence of a thrombocytosis in blood, with a platelet count above 600 × 10⁹/L. Nevertheless, controversy exists regarding this platelet count “cut-off” value and, when RARS-MT was defined, the JAK2 mutation and its importance in the study of myeloproliferative disorders was unknown. We present the results of a Spanish retrospective multicentric study, which includes 76 cases of RARS with associated thrombocytosis (platelet count above 400 × 10⁹/L) at diagnosis (RARS-T), 36 of them with a platelet count above 600 × 10⁹/L. Our aim was to analyze their clinical, analytical and morphological characteristics, and to establish correlations with the JAK2 mutational status. This work is multicentric, with data collected and centralized at Hospital Universitario de Canarias (La Laguna, Spain).     

An exploratory clinical trial of bortezomib in patients with lower risk myelodysplastic syndromes

Myelodysplastic syndromes (MDSs) are characterized by ineffective hematopoiesis and an increased risk of transformation. Few effective therapies are available for lower risk MDS patients, especially after the failure of hypomethylating agents. MDS progenitor cells are dependent on the nuclear factor‐κB (NF‐κB) for survival, which makes it an attractive therapeutic target. As a proteosomal inhibitor, bortezomib is thought to have inhibitory activity against NF‐κB. We designed a proof‐of‐principle study of subcutaneous (SC) bortezomib in lower risk MDS patients with evidence of NF‐κB activation in their bone marrow. Fifteen patients were treated, their median age was 71 (range 56–87), 33% were low and 67% int‐1 by IPSS, median number of prior therapies was 2, all patients were transfusion dependent. Baseline median pp65 percentage was 31% and 11 patients had evidence of ring sideroblasts (RS). SC bortezomib was safe, well tolerated with no excess toxicity. Three patients out of the 15 (20%) had evidence of response with hematologic improvement (HI‐E). Bortezomib caused a decrease in pp65 levels in 7 out of 13 evaluable patients (54%, P = .025). Of interest, unexpectedly, we observed a significant decrease in RS in 7 out of 10 (70%) evaluable patients during treatment. In conclusion, this study suggests that NF‐κB activation, measured by pp65 levels, may be a useful biomarker in MDS. Bortezomib is safe in this patient population but has modest clinical activity. The role of the proteasome in the genesis of RS needs further study.     

Open‐label study of oral CEP‐701 (lestaurtinib) in patients with polycythaemia vera or essential thrombocythaemia with JAK2‐V617F mutation

JAK2‐V617F is central to the pathogenesis of myeloproliferative neoplasms. We examined whether lestaurtinib decreased JAK2‐V617F allele burden and evaluated its clinical benefits and tolerability in patients with polycythaemia vera (PV) and essential thrombocythaemia (ET). This phase 2, open‐label, multicentre study was designed to detect ≥15% reduction in JAK2‐V617F allele burden in 15% of patients. Eligible patients received lestaurtinib 80 mg twice daily for 18 weeks and could participate in a 1‐year extension phase of treatment. Of 39 enrolled patients, 27 (69%) had PV; 12 (31%) had ET. While the pre‐specified responder rate of 15% was not met, lestaurtinib modestly reduced JAK2‐V617F allele burden and reduced spleen size in a subset of patients. Of 37 patients in the full efficacy analysis, 5 (14%) responded clinically. Every patient had ≥1 adverse event, most commonly gastrointestinal (95%). Fifteen patients (38%) experienced serious adverse events; 23 (59%) withdrew due to adverse events. This is the first reported study of JAK2‐inhibitor treatment in patients with PV/ET and highlights both the need for further studies to assess the role of JAK2 inhibition in treatment of PV/ET and the use of JAK2‐V617F as a biomarker for response. This trial was registered at www.clinicaltrials.gov as NCT00586651.     

SF3B1 mutations are prevalent in myelodysplastic syndromes with ring sideroblasts but do not hold independent prognostic value

SF3B1 mutations were recently reported in myelodysplastic syndromes (MDSs), especially in the presence of ring sideroblasts (RSs). We sought to define the interaction between SF3B1 mutations, morphology, karyotype, and prognosis in MDS with more than or equal to 15% RS (MDS-RS). We studied 107 patients with MDS-RS, including 48 with refractory anemia with RS (RARS), 43 with refractory cytopenia with multilineage dysplasia (RCMD)-RS, 11 with refractory anemia with excess blasts-1 (RAEB1)-RS, and 5 with RAEB2-RS. SF3B1 mutations were detected in 53 (～ 50%) patients: 35 RARS (73%), 16 RCMD-RS (37%), and 2 RAEB1-RS (18%). In univariate analysis, the presence of SF3B1 mutations was associated with better overall (P < .01) and leukemia-free (P < .01) survival; however, in both instances, significance was completely accounted for by World Health Organization morphologic risk categorization. In other words, when RARS and RCMD-RS were analyzed separately, there was no additional prognostic value from the presence or absence of SF3B1 mutations.     

Comparing the prognostic value of risk stratifying models for patients with lower‐risk myelodysplastic syndromes: Is one model better?

Some patients classified as having lower‐risk (LR)‐disease by the International Prognostic Scoring System (IPSS) fare more poorly than predicted. We examined the prognostic utility of IPSS, the MD Anderson LR‐Prognostic System (LR‐PSS), and the revised IPSS (IPSS‐R) in a large cohort of patients classified as having IPSS LR‐MDS in the MDS Clinical Research Consortium database. Actual overall survival (OS) was assessed in patients with IPSS LR‐MDS (i.e. low and intermediate‐1) using Kaplan–Meier methods. Harrell's c index (HCI) and Akaike information criteria (AIC) were used to compare the models. Median OS of 1,140 eligible patients was 47 months (95% CI, 44–52). Median follow‐up was 62 months. HCI values indicating the discriminatory power of the models (higher is better) were better for LR‐PSS (0.74, 95% CI, 0.70–0.78) than IPSS‐R (0.64, 95% CI, 0.60–0.67) and IPSS (0.64, 95% CI, 0.60–0.68). Similarly, AIC values indicating the goodness of the fit were better for LR‐PSS than IPSS‐R and IPSS (8,110, 8,147, and 8,150, respectively, lower is better). LR‐PSS assigned 25.1% and 37.4% of patients with IPSS LR‐MDS into LR‐PSS Category 3 and IPSS‐R Categories ≥Intermediate, respectively. Of 291 patients (25.5%) who survived ≤24 months from diagnosis, only 37.1% and 45% were classified as LR‐PSS category 3 and IPSS‐R categories ≥Intermediate, respectively (P = 0.06). While both LR‐PSS and IPSS‐R distinguish groups with varied survival outcome among patients with IPSS LR‐MDS, both tools fail to identify a significant subset with poor OS. Future studies should assess whether patients identified as at increased risk will benefit from earlier interventions with disease‐modifying therapies. Am. J. Hematol. 90:1036–1040, 2015. © 2015 Wiley Periodicals, Inc.     

Clinical significance of regulatory T cells in patients with myelodysplastic syndrome

Objective: Foxp3⁺ regulatory T cells (Tregs) play a central role in maintaining immune tolerance. Their expansion in malignant diseases leads to the suppression of host anti‐tumour responses. In this study, we evaluated the clinical significance of Tregs in patients with myelodysplastic syndrome (MDS). Patients and Methods: We analysed the number of CD4⁺ CD25⁺ Foxp3⁺ Tregs using three‐colour flow cytometry in the peripheral blood of 26 patients with MDS classified according to the World Health Organization classification method into four cases of refractory anaemia and refractory anaemia with ringed sideroblasts (RA/RARS), 15 cases of refractory cytopenia with multilineage dysplasia (RCMD), three cases of refractory anaemia with excess blast‐1 (RAEB‐1) and four cases of refractory anaemia with excess blast‐2 (RAEB‐2). Eighteen healthy volunteers were included as the control group. Results: The mean absolute numbers of Tregs in the RA/RARS group (0.06 × 10⁹/L; 95% CI, 0.02–0.10 × 10⁹/L) and RAEB group (0.06 × 10⁹/L; 95% CI, 0.02–0.10 × 10⁹/L) were significantly higher than that of the control group (0.03 × 10⁹/L; 95% CI, 0.02–0.03 × 10⁹/L) (P < 0.05). However, in the RCMD group, there was no significant difference in the mean absolute number of Tregs (0.03 × 10⁹/L; 95% CI, 0.02–0.04 × 10⁹/L) compared with the control group. Regarding the mean level of the CD8/Foxp3 ratio, there were significant decreases in the RA/RARS group (2.8; 95% CI, 0.7–4.9; P < 0.01), RCMD group (3.4; 95% CI, 2.0–4.4; P < 0.001) and RAEB group (2.1; 95% CI, 1.7–2.5; P < 0.001) compared with the control group (6.1; 95% CI, 5.1–7.0). Conclusions: The expansion of natural CD4⁺ Tregs may contribute to the suppression of CD8 through the Th1‐mediated immune response in MDS. The low CD8/Foxp3 ratio is a characteristic feature in MDS. To determine whether the expansion of CD4⁺ Tregs contributes to the progression of MDS subtypes into more aggressive subtypes, more MDS cases and further follow‐up are required.     

Is refractory anaemia with ring sideroblasts and thrombocytosis (RARS‐T) a necessary or useful diagnostic category?

Both the 2001 World Health Organisation (WHO) classification of haematopoietic neoplasms and the 2008 WHO classification revision include a distinctive diagnostic category, refractory anaemia with ring sideroblasts and thrombocytosis (RARS-T), to describe those rare patients who have both ≥15% ring sideroblasts and a sustained elevated platelet count. Recently, it has become clear that patients meeting WHO criteria for RARS-T have clonal JAK2^V617F and MPL^W515 mutations at a similar rate to essential thrombocythaemia (ET). Given that the provisional classification of RARS-T as a myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndrome, rather than as a form of MPN (i.e., ET), rests principally upon the presence of ring sideroblasts, which are a non-specific morphological finding, these new molecular results prompt reconsideration of the necessity for a distinctive RARS-T category. Here we review the historical developments that led up the definition of RARS-T as a disease entity, and we discuss conceptual understanding of RARS-T and arguments against continued use of RARS-T as a separate diagnostic category.     

Bmi-1 is useful as a novel molecular marker for predicting progression of myelodysplastic syndrome and patient prognosis

The International Prognostic Scoring System (IPSS) has been widely used to predict the prognosis of patients with myelodysplastic syndrome (MDS). However, IPSS does not always provide a sufficiently precise evaluation of patients to allow the appropriate choice of clinical interventions. Here, we analyzed the expression of Bmi-1, which is required to regulate the self-renewal in CD34+ cells from 51 patients with cases of MDS and acute myeloid leukemia preceded by MDS (MDS-AML). Higher positivity rate of Bmi-1 was preferentially seen in refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEB-T), and MDS-AML compared with refractory anemia (RA) and RA with ringed sideroblasts (RARS). IPSS score was positively correlated with the percentage of Bmi-1 expression. Patients with RA and RARS with a higher percentage of Bmi-1+ cells showed disease progression to RAEB. Here, we propose Bmi-1 as a novel molecular marker to predict the progression and prognosis of MDS.     

Prevalence of the JAK2V617F mutation in Chinese patients with Budd-Chiari syndrome and portal vein thrombosis: a prospective study

Background and Aim: Whether routine screening for the JAK2V617F mutation should be performed in Chinese patients with Budd‐Chiari syndrome (BCS) and portal vein thrombosis (PVT) is unclear. Therefore, we aimed to evaluate the prevalence of the JAK2V617F mutation in such patients and to explore the risk factors associated with the mutation. Methods: All consecutive patients with BCS and PVT diagnosed between September 2009 and May 2011 were prospectively enrolled in the observational study and underwent the JAK2V617F mutation detection. Results: Prevalence of the JAK2V617F mutation was 4.3% (4/92) in patients with primary BCS, 26.6% (17/64) in non‐malignant and non‐cirrhotic patients with PVT, and 1.4% (1/71) in cirrhotic patients with PVT. All BCS patients with the JAK2V617F mutation had both platelet count (PLT) of above 100 × 10⁹/L (range, 107–188 × 10⁹/L) and splenomegaly. In non‐malignant and non‐cirrhotic patients with PVT, higher PLT and older ages were the independent predictors of the JAK2V617F mutation. Further, the difference in PLT between the patients with and without the mutation displayed greater significance in the subgroup of patients with splenomegaly (P < 0.0001), but the statistical significance disappeared in the subgroup of patients with splenectomy (P = 0.1312). Conclusions: The low prevalence of the JAK2V617F mutation in patients with BCS suggests that myeloproliferative neoplasm should be an uncommon etiological factor of BCS in China. Routine screening for the JAK2V617F mutation might be recommended in non‐malignant and non‐cirrhotic patients with PVT, but not in cirrhotic patients with PVT. The coexistence of higher PLT and splenomegaly might be closely associated with the JAK2V617F mutation.