Essential Thrombocythemia Research Articles

Top Ten Tips Palliative Care Clinicians Should Know About Caring for Patients with Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs) are a group of rare chronic progressive blood cancers that vary widely in clinical presentation, yet all patients have a risk of disease progression and thrombotic complications. Diseases include primary myelofibrosis, polycythemia vera, and essential thrombocythemia. With current treatment approaches, most patients live a prolonged life, but many experience a complex of symptoms that negatively influence their functional status and quality of life. Although significant advances have been made in preventing arterial and venous complications while mitigating inflammatory processes, comprehensive palliative care can help address unmet complex physical and psychosocial needs on a long-term basis. This article, created by a multidisciplinary group of providers, offers an overview of MPNs so palliative care clinicians can better support patients with these hematologic cancers.

Transformation into acute myeloid leukemia with t(8;21)(q22;q22.1); RUNX1::RUNX1T1 from JAK2-mutated essential thrombocythemia: a case report

BackgroundBlast transformation is a rare but well-recognized event in Philadelphia-negative myeloproliferative neoplasms associated with a poor prognosis. Secondary acute myeloid leukemias evolving from myeloproliferative neoplasms are characterized by a unique set of cytogenetic and molecular features distinct from de novo disease. t(8;21) (q22;q22.1); RUNX1::RUNX1T1, one of the most frequent cytogenetic abnormalities in de novo acute myeloid leukemia, is rarely observed in post-myeloproliferative neoplasm acute myeloid leukemia. Here we report a case of secondary acute myeloid leukemia with t(8;21) evolving from JAK2-mutated essential thrombocythemia.Case presentationThe patient was a 74-year-old Japanese woman who was referred because of thrombocytosis (platelets 1046 × 109/L). Bone marrow was hypercellular with increase of megakaryocytes. Chromosomal analysis presented normal karyotype and genetic test revealed JAK2 V617F mutation. She was diagnosed with essential thrombocythemia. Thrombocytosis had been well controlled by oral administration of hydroxyurea; 2 years after the initial diagnosis with ET, she presented with leukocytosis (white blood cells 14.0 × 109/L with 82% of blasts), anemia (hemoglobin 91 g/L), and thrombocytopenia (platelets 24 × 109/L). Bone marrow was hypercellular and filled with 80% of myeloperoxidase-positive blasts bearing Auer rods. Chromosomal analysis revealed t(8;21) (q22;q22.1) and flow cytometry presented positivity of CD 13, 19, 34, and 56. Molecular analysis showed the coexistence of RUNX1::RUNX1T1 chimeric transcript and heterozygous JAK2 V617F mutation in leukemic blasts. She was diagnosed with secondary acute myeloid leukemia with t(8;21)(q22;q22.1); RUNX1::RUNX1T1 evolving from essential thrombocythemia. She was treated with combination chemotherapy with venetoclax and azacytidine. After the first cycle of the therapy, blasts disappeared from peripheral blood and decreased to 1.4% in bone marrow. After the chemotherapy, RUNX1::RUNX1T1 chimeric transcript disappeared, whereas mutation of JAK2 V617F was still present in peripheral leukocytes.ConclusionsTo our best knowledge, the present case is the first one with JAK2 mutation preceding the acquisition of t(8;21). Our result suggests that t(8;21); RUNX1::RUNX1T1 can be generated as a late event in the progression of JAK2-mutated myeloproliferative neoplasms. The case presented typical morphological and immunophenotypic features associated with t(8;21) acute myeloid leukemia.

C-Mannosyl tryptophan is a novel biomarker for thrombocytosis of myeloproliferative neoplasms

C-Mannosyl tryptophan (CMW), a unique glycosylated amino acid, is considered to be produced by degradation of C-mannosylated proteins in living organism. Although protein C-mannosylation is involved in the folding and secretion of substrate proteins, the pathophysiological function in the hematological system is still unclear. This study aimed to assess CMW in the human hematological disorders. The serum CMW levels of 94 healthy Japanese workers were quantified using hydrophilic interaction liquid chromatography. Platelet count was positively correlated with serum CMW levels. The clinical significance of CMW in thrombocytosis of myeloproliferative neoplasms (T-MPN) including essential thrombocythemia (ET) were investigated. The serum CMW levels of the 34 patients with T-MPN who presented with thrombocytosis were significantly higher than those of the 52 patients with control who had other hematological disorders. In patients with T-MPN, serum CMW levels were inversely correlated with anemia, which was related to myelofibrosis (MF). Bone marrow biopsy samples were obtained from 18 patients with ET, and serum CMW levels were simultaneously measured. Twelve patients with bone marrow fibrosis had significantly higher CMW levels than 6 patients without bone marrow fibrosis. Collectively, these results suggested that CMW could be a novel biomarker to predict MF progression in T-MPN.

Mechanobiology and Primary Cilium in the Pathophysiology of Bone Marrow Myeloproliferative Diseases.

Philadelphia-Negative Myeloproliferative neoplasms (MPNs) are a diverse group of blood cancers leading to excessive production of mature blood cells. These chronic diseases, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), can significantly impact patient quality of life and are still incurable in the vast majority of the cases. This review examines the mechanobiology within a bone marrow niche, emphasizing the role of mechanical cues and the primary cilium in the pathophysiology of MPNs. It discusses the influence of extracellular matrix components, cell-cell and cell-matrix interactions, and mechanosensitive structures on hematopoietic stem cell (HSC) behavior and disease progression. Additionally, the potential implications of the primary cilium as a chemo- and mechanosensory organelle in bone marrow cells are explored, highlighting its involvement in signaling pathways crucial for hematopoietic regulation. This review proposes future research directions to better understand the dysregulated bone marrow niche in MPNs and to identify novel therapeutic targets.

Chronic systemic thrombosis of unknown etiology with concurrent essential thrombocythemia and recurrent stroke: A case report

Here, we report a male patient under hypercoagulable state of unproven etiology, who used to present with recurrent thrombotic episodes since young age after he stopped taking anticoagulant. At the age of 73, he was detected to have essential thrombocythemia while grappling with recurrent strokes. On both occasions, he presented with a basilar thrombus. His National Institutes of Health Stroke Scale (NIHSS) score improved from 18 to 2 on the first occasion and from 17 to 2 sixteen days later on the second occasion. Thrombolysis was done on both occasions, but endovascular therapy was not done on either occasion due to chronicity of the thrombus and remarkably improved NIHSS post-thrombolysis. For patients with recurrent thrombotic events of undetermined etiology, an anticoagulant should be indicated. Repeat thrombolysis can be performed without endovascular therapy within a brief gap of 16 days, even in stroke patients with moderate to high NIHSS.

Evaluation of Philadelphia-negative myeloproliferative neoplasms in Erbil Iraq; analysis of JAK 2, CALR, and MPL mutations

Introduction: The prevalence of Janus kinase 2 V617F, Jak 2-Exon12, calreticulin (CALR) gene mutations and myeloproliferative leukemia mutations in myeloproliferative neoplasms (MPNs) without BCR-ABL1 gene fusion rearrangement in Iraq remains unknown due to inadequate data. Objectives: The aim of this study was to ascertain the prevalence of these mutations and assess the clinical characteristics of polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) in Erbil, Iraq. Patients and Methods: In this cross-sectional study, 80 patients were evaluated for the presence of JAK 2 V617, CALR, and MPL mutations. Specific primers were utilized to amplify MPNs-associated mutations (JAK 2 V617F, Jak 2 -Exon12, CALR, and MPL) using DNA extracted from whole blood. Results: The presence of the JAK 2 V617F mutation was identified in 96% of patients diagnosed with PV and 35% of patients diagnosed with ET. Additionally, JAK 2 exon 12 was detected in 4% of PV patients. CALR mutation was identified in 65% of ET patients. No detection of MPL mutation was observed. A higher prevalence of the CALR mutation was observed in younger age groups, whereas the JAK 2 V617F mutation was predominantly found in older age groups. Conclusion: The incorporation of genetic tests for JAK 2 V617F, JAK 2 exon 12, MPL exon 10, and CALR exon 9 significantly improves the diagnostic effectiveness for BCR ABL1-gene fusion negative MPNs.

Cardiovascular Risk in Philadelphia-Negative Myeloproliferative Neoplasms: Mechanisms and Implications-A Narrative Review.

Myeloproliferative neoplasms (MPNs), encompassing disorders like polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are characterized by clonal hematopoiesis without the Philadelphia chromosome. The JAK2 V617F mutation is prevalent in PV, ET, and PMF, while mutations in MPL and CALR also play significant roles. These conditions predispose patients to thrombotic events, with PMF exhibiting the lowest survival among MPNs. Chronic inflammation, driven by cytokine release from aberrant leukocytes and platelets, amplifies cardiovascular risk through various mechanisms, including atherosclerosis and vascular remodeling. Additionally, MPN-related complications like pulmonary hypertension and cardiac fibrosis contribute to cardiovascular morbidity and mortality. This review consolidates recent research on MPNs' cardiovascular implications, emphasizing thrombotic risk, chronic inflammation, and vascular stiffness. Understanding these associations is crucial for developing targeted therapies and improving outcomes in MPN patients.

The investigation of janus kinase 2 and calreticulin mutations in patients with essential thrombocytosis

Aims: The aims of this study were to investigate the frequency of Janus Kinase 2 (JAK2) and calreticulin (CALR) mutations in patients with essential thrombocytosis (ET) and primary myelofibrosis (PMF) and to compare the data of each group with JAK2 and CALR mutations (+) and (-). Methods: The research group consisted of 80 patients with chronic myeloproliferative disease (CMPD) followed in Gazi University Hospital of Medical Faculty, Hematology Clinic. Results: Of the patients included in the study, 66.2% had ET and 33.8% had PMF. JAK2 mutation (+) was detected in 60% and CALR mutation (+) was found in 22.5% of the patients. JAK2 mutation (+) was detected in 60.4% of patients with ET and 59.3% of patients with PMF. In JAK2 (-) patients, CALR was detected as (+) in 11 patients (52.4%) with ET and 7 patients (63.6%) with PMF. Conclusion: Studies in the literature have shown that the incidence of CALR mutations in patients with CMPD is between 28% and 80% and that the mutation is mostly seen in patients with ET. As a result of our study, it was concluded that the laboratory findings of patients with CALR mutations (+) were similar to those in the literature and were more common in women and ET patients.

Treatment comparison of hydroxyurea versus ruxolitinib in essential thrombocythaemia: A matched-cohort analysis.

Hydroxyurea is the preferred first-line cytoreductive treatment for high-risk essential thrombocythaemia (ET), but many patients are intolerant or refractory to hydroxyurea. Ruxolitinib has been shown to improve symptoms in patients with ET. This post hoc analysis compared the clinical outcomes of patients with ET who received hydroxyurea only with those who switched from hydroxyurea to ruxolitinib due to intolerance/resistance to hydroxyurea. Patients with ET refractory/intolerant to hydroxyurea treated with ruxolitinib in a completed phase 2 study (HU-RUX) were propensity score matched with patients who received hydroxyurea only in an observational study (HU). Changes in leukocyte and platelet counts were reported at 6-month intervals during the 48-month follow-up. Following propensity score matching, 37 patients were included for analysis in each cohort. Mean (standard deviation [SD]) leukocyte and platelet counts at index were higher for HU-RUX versus HU (leukocyte: 9.3 [5.1] vs. 6.8 [3.1]×109/L; platelet: 1027.4 [497.8] vs. 513.9 [154.7]×109/L), both of which decreased significantly from index to 6 months through to 48 months in HU-RUX (mean [SD] change from index at 6 months-leukocyte: -1.8 [4.6]×109/L; platelet: -391.7 [472.9]×109/L; at 48 months-leukocyte: -3.8 [5.3]×109/L; platelet: -539.0 [521.8]×109/L), but remained relatively stable in HU (mean [SD] change from index at 6 months-leukocyte: 0 [1.8]×109/L; platelet: -5.7 [175.3]×109/L; at 48 months-leukocyte: -0.1 [2.7]×109/L; platelet: -6.9 [105.1]×109/L). In conclusion, these results demonstrate that switching from hydroxyurea to ruxolitinib in patients with ET who are intolerant or refractory to hydroxyurea could improve abnormal haematologic values similar to those who receive first-line hydroxyurea.

A 72-year-old Woman with Dyspnea and Thrombocytosis

<p>原發性血小板增多症的臨床表徵並不典型且早期診斷不易，往往多數病人於診斷前已發生動靜脈血栓形成及出血併發症。本個案一位72歲女性，有高血壓及胃食道逆流病史並按時門診追蹤服藥，五天前注射新冠疫苗後，呼吸喘、乾咳併胸悶至診所就醫未改善，於急診初步診斷急性支氣管炎。入院後感心悸且胸悶，藉由病史詢問、檢驗及理學檢查，顯示心肌酵素正常但心電圖呈現陣發性心室上心搏過速，安排冠狀動脈血管攝影攝影後排除急性心肌梗塞，但呼吸急促未見好轉呈現低血氧，經胸腔電腦斷層為肺栓塞。疑似新冠疫苗後引起的免疫併發症，直到右手食指及中指末梢腫、痛且發紺症狀出現，筆者再次重新檢視病史資料，發現血小板異常，透過骨髓穿刺切片是發現巨核細胞（megakaryocyte）增生，病理報告判斷為骨髓增生性腫瘤，基因檢測結果為JAK2V617F 突變，最後確診是原發性血小板增多症併發肺栓塞，接受Hydroxyurea合併口服抗凝血劑治療，症狀改善且血小板數值趨於穩定。藉此案例分享提醒當發現病人有不明血栓產生時須考慮將相關血液疾病列入鑑別診斷，期能及早發現疾病，掌握治療時機。</p> <p> </p><p>The clinical symptoms of essential thrombocythemia are not typical and early diagnosis is difficult.Most patients have arteriovenous thrombosis and bleeding complications before diagnosis. In this case, a 72-year-old woman had a history of hypertension and gastroesophageal reflux and was taking medication regularly at the outpatient clinic. After being injected with the COVID-19 vaccine five days ago, her breathing, dry cough, and chest tightness did not improve when she went to the clinic. She was initially diagnosed with acute bronchitis in the emergency department. After being admitted to the hospital, she felt palpitations and chest tightness. The medical history, examination and physical examination showed that myocardial enzymes were normal, but the electrocardiogram showed Parox-ysmal supraventricular tachycardia. Coronary angiography was arranged to rule out acute myocardial infarction, but the shortness of breath persisted with hypoxemia, and the computed tomography of the chest showed pulmonary embolism. Immune complications caused by the COVID-19 vaccine were suspected, symptoms of swelling, pain and cyanosis appeared in the distal part of the right index fin-ger and middle finger appeared. The author re-examined the medical history data and found abnormal platelets. Through bone marrow aspiration and sectioning, megakaryocyte hyperplasia was found. Pa-thology report determined that the patient suffered from myeloproliferative neoplasm, and the genetic test result was the JAK2V617F mutation. The patient was finally diagnosed with essential thrombocythe-mia complicated by pulmonary embolism. She was treated with Hydroxyurea combined with oral an-ticoagulants. The symptoms improved and the platelet level stabilized. This case serves as a reminder that when a patient is found to have unknown thrombosis, related blood diseases must be considered in the differential diagnosis, so that the disease can be detected early and proper treatments can be pro-vided.</p> <p> </p>

Increased mRNA expression for serotonin receptor 1B (HTR1B) is associated with thrombosis in BCR::ABL1-negative myeloproliferative neoplasms.

BCR::ABL1-negative myeloproliferative neoplasms (MPNs) are clonal haematopoietic stem cell disorders characterized by specific driver mutations and an increased risk of both macrothrombosis and microthrombosis. Serotonin receptor type 1B (HTR1B) was found to be expressed by various solid tumours, and also primary bone marrow mononuclear cells from myelodysplastic neoplasm and acute myeloid leukaemia patients, representing a potential therapeutic target. In this study we assessed for the first time the expression levels of HTR1B mRNA in the peripheral blood mononuclear cells (PBMC) of 85 newly diagnosed MPN patients, consisting of 28 polycythemia vera, 25 essential thrombocythemia and 32 primary myelofibrosis cases. Levels of HTR1B expression between MPN subtypes and control group were not significantly different. However, at clinical data examination, it was observed that MPN patients with a recent history of major thrombosis and/or signs of impaired microcirculation exhibited significantly higher HTR1B expression levels compared to non-thrombotic MPNs and control group. Moreover, thrombotic MPN patients had significantly higher HTR1B expression than patients with recent thrombosis and absence of MPN diagnostic criteria. These findings suggest that increased levels of HTR1B expression in PBMC might be associated with thrombosis in MPN patients, but larger studies are needed for confirmation, including testing of the receptor protein expression level.

Liver and spleen shear-wave elastography in the diagnosis and severity staging of myeloproliferative diseases and myelofibrosis.

Spleen and liver stiffness, investigated by VCTE (Vibration-Controlled Transient Elastography), have been associated with marrow fibrosis in patients with myeloproliferative neoplasms (MPNs). Tissue stiffness can be assessed by shear wave point (pSWE) and bidimensional elastography (2DSWE). Spleen stiffness (SS)values were higher in Myelofibrosis (MF) and Polycythemia Vera (PV) compared to Essential Thrombocythemia (ET). We aimed to identify SWE differences between MPN patients and healthy volunteers; to evaluate specific SWE features in patients with MF, PV and ET; to establish a correlation with bone marrow fibrosis in patients with myeloproliferative disease. Patients with myeloproliferative disease and healthy volunteers performed evaluation of spleen and liver stiffness (LS)by pSWE and 2DSWE. A total of 218 subjects were included: 143 with myeloproliferative disease (64 MF, 29.4%, 33 PV, 15.1% and 46 ET, 21.1%), and 75 (34.4%) healthy volunteers. Compared to volunteers, MF patients had greater spleen (pSWE 40.9 vs. 26.3kPa, p < 0.001; 2DSWE 34.9 vs. 20.1kPa, p < 0.001), and liver stiffness (pSWE 7.72 vs. 5.52kPa, p < 0.001; 2DSWE 6.96 vs. 5.01kPa, p < 0.001). In low (0-1) (n = 81, 60.4%) versus high-grade bone marrow fibrosis (2-3) (n = 42, 39.6%), is evident a higher median stiffness in patients with higher grades of fibrosis both for liver (pSWE 5.2 vs. 6.65kPa; 2DSWE 5.1 vs. 6.05kPa) and spleen (pSWE 27.2 vs. 37.9kPa, 2DSWE 21.7 vs 30.75kPa-p < 0.001 in both). SWE evaluation distinguishes MF patients from HV and ET/PV and may help in MPN diagnosis. LS and SS values are associated with bone marrow fibrosis grade.

Sexually Transmitted Infections Surveillance in Pakistan.

Inflammatory bowel disease (IBD) and myeloproliferativeneoplasms (MPNs) are both chronic disorders in whosepathogenesis low-grade chronic inflammation plays acentral contribution.1-3 IBD is characterised by chronicinflammation of the digestive tract, while MPNs arecharacterized by an overproduction of terminallydifferentiated myeloid cells.1,3 IBD may present itself mainlyas ulcerative colitis (UC) or Crohn’s disease (CD) while theclassical Philadelphia-negative MPNs comprisepolycythemia vera (PV), essential thrombocythemia (ET)and primary/secondary myelofibrosis (MF).1,3 A recentcohort study found that subjects with MPNs have a 2.4-foldincreased risk of developing IBD compared to individualswithout MPNs. The risk of developing IBD was highestwithin the first year after the diagnosis of MPN and afterfive years of being diagnosed with an MPN. However, therewas a lower risk of developing IBD between the first yearand fifth year of being diagnosed with an MPN.4 Thesefindings suggest that there may be a common underlyingmechanism that drives the pathogenesis of both IBD andMPNs. Moreover, alterations of the gut microbiome havebeen described both in MPNs and IBD, possibly in directrelationship with the high concentrations of proinflammatorycytokines measured in these disorders.1,5 Continued...

Predictive significance of high neutrophil ratio for thrombosis in myeloproliferative neoplasms: JSH-MPN-R18 subanalysis.

Thrombosis in myeloproliferative neoplasms (MPNs) is an important clinical problem, and risk-stratified management is essential. To identify the clinical characteristics of thrombosis in patients with MPNs, a nationwide multi-institutional retrospective analysis (JSH-MPN-R18) was conducted. The aim of the present study was to perform a sub-analysis of JSH-MPN-R18 findings to clarify the predictive parameters for thrombosis among complete blood count (CBC) results. Among the patients enrolled in JSH-MPN-R18, those with essential thrombocythemia (ET; n = 1152) and polycythemia vera (PV; n = 456) were investigated. We analyzed and compared CBC parameters between patients with and those without any thrombotic events using Welch's T-test. Statistical analyses were performed using the R statistical software. Thrombotic events were observed in 74 patients with ET. In multivariate analysis, only the neutrophil ratio was slightly but significantly higher for ET patients with thrombosis than for those without (p < 0.05). Of note, the absolute neutrophil count (aNeu) was considered a useful predictive tool for thrombosis among patients classified as low-risk according to the revised International Prognostic Score of Thrombosis for Essential Thrombocythemia. Among PV patients, those with thrombosis showed significantly higher hematocrit and aNeu than did those without thrombosis. As a thrombosis-associated factor, the neutrophil ratio was slightly but significantly elevated in patients with ET. This myeloid skew might reflect a higher value of JAK2 V617F allelic frequency in patients with ET with thrombosis; this was not clarified in JSH-MPN-R18. Further accumulation of evidence, including genetic information for JAK2 and other passenger mutations, is warranted.

The Burden of symptoms and Quality of life of Filipino patients with Myeloproliferative neoplasm: A Multicenter Cross-sectional survey.

Myeloproliferative neoplasms (MPN) are hematologic malignancies characterized by cellular proliferation of one or more hematopoietic cell lines. Management has been focused on blood count control but addressing relief from symptoms and providing a better quality of life (QOL) are equally important in the care of these patients. The MPN Symptom Assessment Form-Total Symptom Score (MPN-SAF TSS) is used to determine symptoms at baseline and during treatment. Understanding the symptom burden is important in developing a holistic management plan for MPN. Hence, this study aimed to determine the symptom burden and QOL of Filipino patients with MPN. Using a validated Filipino version of the MPN-SAF-TSS questionnaire and the University of the Philippines-Department of Health QOL (UP-DOH QOL) questionnaire, a cross-sectional survey of consecutive patients with MPN from two public and two private tertiary hospitals was conducted. We purposively sampled adults, newly diagnosed or previously diagnosed with polycythemia vera (PV), essential thrombocythemia (ET), or myelofibrosis (MF). The mean scores were compared with the type of MPN using analysis of variance. Linear regression was done to determine the association of patients' characteristics to the mean symptom burden and QOL scores, while logistic regression was used to determine the association of patient and disease characteristics with the level of symptom severity and QOL. A total of 167 (63 PV, 66 ET, and 38 MF) patients were surveyed from four centers. The mean overall symptom burden score was 24.41 (standard deviation [SD]=18.91) with MF having the highest score at 28.53, followed by PV at 23.75 and ET at 22.67. The majority (80.24%) had a high QOL with a mean global QoL score of 84.92 (SD=16.75). Comparison of individual scores showed bone pain and weight loss were significantly higher in patients with MF compared to PV (p=0.0002) and ET (p=0.032); while pruritus was significantly higher in PV compared to ET and MF (p=0.043). Logistic regression analysis showed female sex and being newly diagnosed (adjusted odds ratio [aOR] 11.22, 95% confidence interval [CI] 2.32-54.25) were associated with high symptom burden while having a controlled blood count (aOR 0.26, 95% CI 0.10-0.71) was associated with low symptom burden and high QOL. The majority of the participants were symptomatic with moderate to severe symptom burden. While no statistically significant difference was seen among the three types of MPN in terms of overall mean symptom score, patients with MF were more likely to have a severe symptom burden while patients with ET had the least symptoms. Despite having symptoms, QOL was regarded as high. QoL was significantly higher among those with PV or ET than those with MF. Our study highlighted the utility of a validated symptom scoring system in determining the symptom burden and who would benefit from pharmacologic/non-pharmacologic symptom management. Results emphasized incorporating symptom scoring in clinical practice and going beyond blood counts in caring for our patients with MPN.

Clinical utility of investigations in triple-negative thrombocytosis: A real-world, multicentre evaluation of UK practice.

Diagnosis of essential thrombocythaemia (ET) is challenging in patients lacking JAK2/CALR/MPL mutations. In a retrospective evaluation of 320 patients with 'triple-negative thrombocytosis', we assessed utility of bone marrow histology (90.9% of patients) and myeloid gene panel (MGP, 55.6%). Supportive histology ('myeloproliferative neoplasm-definite/probable', 36.8%) was associated with higher platelet counts and varied between centres. 14.6% MGP revealed significant variants: 3.4% JAK2/CALR/MPL and 11.2% other myeloid genes. Final clinical diagnosis was strongly predicted by histology, not MGP. 23.7% received cytoreduction (17.6% under 60 years). Real-world 'triple-negative' ET diagnosis currently depends heavily on histology; we advocate caution in MGP-negative cases and that specific guidelines are needed.

Initiating-clone analysis in patients with acute myeloid leukemia secondary to essential thrombocythemia

Most of essential thrombocythemia (ET) patients have the clone harboring a mutation in one of the JAK2, CALR, or MPL gene, and these clones generally acquire additional mutations at transformation to acute myeloid leukemia (AML). However, the proliferation of triple-negative clones has sometimes been observed at AML transformation. To clarify the clonal evolution of ET to AML, we analyzed paired samples at ET and AML transformation in eight patients. We identified that JAK2-unmutated AML clones proliferated at AML transformation in three patients in whom the JAK2-mutated clone was dominant at ET. In two patients, TET2-mutated, but not JAK2-mutated, clones might be common initiating clones for ET and transformed AML. In a patient with JAK2-mutated ET, SMARCC2, UBR4, and ZNF143, but not JAK2, -mutated clones proliferated at AML transformation. Precise analysis using single-cell sorted CD34+/CD38- fractions suggested that ET clone with JAK2-mutated and AML clone with TP53 mutation was derived from the common clone with these mutations. Although further study is required to clarify the biological significance of SMARCC2, UBR4, and ZNF143 mutations during disease progression of ET and AML transformation, the present results demonstrate the possibility of a common initial clone involved in both ET and transformed AML.

Myeloproliferative Neoplasms Transcriptome Reveals Pro-Inflammatory Signature and Enrichment in Peripheral Blood Monocyte-Related Genes

Myeloproliferative neoplasms (MPN) are hematological diseases associated with genetic driver mutations in the JAK2, CALR, and MPL genes and exacerbated oncoinflammatory status. Analyzing public microarray data from polycythemia vera (n = 41), essential thrombocythemia (n = 21), and primary myelofibrosis (n = 9) patients’ peripheral blood by in silico approaches, we found that pro-inflammatory and monocyte-related genes were differentially expressed in MPN patients’ transcriptome. Genes related to cell activation, secretion of pro-inflammatory and pro-angiogenic mediators, activation of neutrophils and platelets, coagulation, and interferon pathway were upregulated in monocytes compared to controls. Together, our results suggest that molecular alterations in monocytes may contribute to oncoinflammation in MPN.

Multi-omics differences in the bone marrow between essential thrombocythemia and prefibrotic primary myelofibrosis

Essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre-PMF) are Philadelphia chromosome-negative myeloproliferative neoplasms. These conditions share overlapping clinical presentations; however, their prognoses differ significantly. Current morphological diagnostic methods lack reliability in subtype differentiation, underlining the need for improved diagnostics. The aim of this study was to investigate the multi-omics alterations in bone marrow biopsies of patients with ET and pre-PMF to improve our understanding of the nuanced diagnostic characteristics of both diseases. We performed proteomic analysis with 4D direct data-independent acquisition and microbiome analysis with 2bRAD-M sequencing technology to identify differential protein and microbe levels between untreated patients with ET and pre-PMF. Laboratory and multi-omics differences were observed between ET and pre-PMF, encompassing diverse pathways, such as lipid metabolism and immune response. The pre-PMF group showed an increased neutrophil-to-lymphocyte ratio and decreased high-density lipoprotein and cholesterol levels. Protein analysis revealed significantly higher CXCR2, CXCR4, and MX1 levels in pre-PMF, while APOC3, APOA4, FABP4, C5, and CFB levels were elevated in ET, with diagnostic accuracy indicated by AUC values ranging from 0.786 to 0.881. Microbiome assessment identified increased levels of Mycobacterium, Xanthobacter, and L1I39 in pre-PMF, whereas Sphingomonas, Brevibacillus, and Pseudomonas_E were significantly decreased, with AUCs for these genera ranging from 0.833 to 0.929. Our study provides preliminary insights into the proteomic and microbiome variations in the bone marrow of patients with ET and pre-PMF, identifying specific proteins and bacterial genera that warrant further investigation as potential diagnostic indicators. These observations contribute to our evolving understanding of the multi-omics variations and possible mechanisms underlying ET and pre-PMF.

A rare presentation of essential thrombocytosis masked as vasculitis

This case study presents the clinical journey of a 37-year-old woman who previously experienced gangrene in her fingers and toes. Initial assessments revealed elevated total white blood cell count and platelets, coupled with low hemoglobin levels. Despite normal inflammatory markers and negative results for antiphospholipid syndrome, antinuclear antibodies, and anti-neutrophil cytoplasmic antibodies, arterial Doppler imaging displayed no abnormalities. Suspecting vasculitis, the patient was initially treated with steroids and aspirin. However, subsequent investigations revealed essential thrombocytosis, a myeloproliferative disorder, confirmed by a positive JAK2 gene mutation. This case underscores the complexity of diagnosing rare hematological disorders and the importance of comprehensive evaluations for accurate treatment strategies.