Myeloproliferative Research Articles

Perioperative outcomes in patients with myeloproliferative neoplasms: a multicentric analysis of 354 surgical procedures

Perioperative outcomes in patients with myeloproliferative neoplasms: a multicentric analysis of 354 surgical procedures

Myeloproliferative Neoplasms and Dementia Risk: A Population-Based Cohort Study.

ABSTRACTObjectivesTo estimate dementia risk for persons diagnosed with Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs), which serve as a human chronic inflammation model.MethodsWe identified 9895 individuals in Denmark newly diagnosed with MPNs from 1995 to 2017; matched them 10:1 by age and sex with a general population cohort of 95 770 individuals; and followed them until dementia identification, death, emigration, or December 31, 2018. We applied a Cox proportional‐hazards regression model to estimate the cause‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia. We included control diseases, like chronic lymphocytic leukemia (CLL), which is not characterized by chronic inflammation.ResultsPatients with MPNs showed a 1.15‐fold (95% CI: 1.04–1.27) increased incidence of dementia compared with members of the general population. Associations were stronger for men with MPNs (HR: 1.40, 95% CI: 1.19–1.63) than for women (HR: 1.02, 95% CI: 0.89–1.15). Patients with CLL showed a decreased dementia incidence (HR: 0.81, 95% CI: 0.72–0.90). The findings for CLL could be explained by depletion‐of‐susceptibles bias, suggesting that the findings for MPNs were underestimated by a similar bias.ConclusionsThe findings support MPNs as risk factors for dementia and the role of chronic inflammation in dementia development.

New advances in the role of JAK2 V617F mutation in myeloproliferative neoplasms.

The JAK2 V617F mutation is the most common driver gene in myeloproliferative neoplasm (MPN), which means that the JAK/STAT signaling pathway is persistently activated independent of cytokines, and plays an important part in the onset and development of MPN. The JAK inhibitors, although widely used in the clinical practice, are unable to eradicate MPN. Therefore, the unavoidable long-term treatment poses a serious burden for patients with MPN. It is established that the JAK2 V617F mutation, in addition its role in the JAK/STAT pathway, can promote cell proliferation, differentiation, anti-apoptosis, DNA damage accumulation, and other key biologic processes through multiple pathways. Other than that, the JAK2 V617F mutation affects the cardiovascular system through multiple mechanisms. Although JAK inhibitors cannot eradicate MPN cells, the combined use of JAK inhibitors and other drugs may have surprising effects. This requires an in-depth understanding of the mechanism of action of the JAK2 V617F mutation. In this review, the authors explored the role of the JAK2 V617F mutation in MPN from multiple aspects, including the mechanisms of non-JAK/STAT pathways, the regulation of cellular methylation, the induction of cellular DNA damage accumulation, and effects on the cardiovascular system, with the objective of providing valuable insights into multidrug combination therapy for MPN.

Selective targeting of mutated calreticulin by the monoclonal antibody INCA033989 inhibits oncogenic function of MPN

AbstractMutations in calreticulin (mutCALR) are the second most common drivers of myeloproliferative neoplasms (MPNs) and yet, the current therapeutic landscape lacks a selective agent for mutCALR-expressing MPNs. Here, we show that the monoclonal antibody INCA033989 selectively targets mutCALR-positive cells. INCA033989 antagonized mutCALR-driven signaling and proliferation in engineered cell lines and primary CD34+ cells from patients with MPN. No antibody binding or functional activity was observed in the cells lacking mutCALR. In a mouse model of mutCALR-driven MPN, treatment with an INCA033989 mouse surrogate antibody effectively prevented the development of thrombocytosis and accumulation of megakaryocytes in the bone marrow. INCA033989 reduced the pathogenic self-renewal of mutCALR-positive disease-initiating cells in both primary and secondary transplantations, illustrating its disease-modifying potential. In summary, we describe a novel mutCALR-targeted therapy for MPNs, a monoclonal antibody that selectively inhibits the oncogenic function of MPN cells without interfering with normal hematopoiesis.

The Role of Mutated Calreticulin in the Pathogenesis of BCR-ABL1-Negative Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs) are characterized by increased proliferation of myeloid lineages in the bone marrow. Calreticulin (CALR) 52 bp deletion and CALR 5 bp insertion have been identified in essential thrombocythemia (ET) and primary myelofibrosis (PMF). There is not much data on the crosstalk between mutated CALR and MPN-related signaling pathways, such as JAK/STAT, PI3K/Akt/mTOR, and Hedgehog. Calreticulin, a multifunctional protein, takes part in many cellular processes. Nevertheless, there is little data on how mutated CALR affects the oxidative stress response and oxidative stress-induced DNA damage, apoptosis, and cell cycle progression. We aimed to investigate the role of the CALR 52 bp deletion and 5 bp insertion in the pathogenesis of MPN, including signaling pathway activation and functional analysis in CALR-mutated cells. Our data indicate that the JAK/STAT and PI3K/Akt/mTOR pathways are activated in CALR-mutated cells, and this activation does not necessarily depend on the CALR and MPL interaction. Moreover, it was found that CALR mutations impair calreticulin function, leading to reduced responses to oxidative stress and DNA damage. It was revealed that the accumulation of G2/M-CALR-mutated cells indicates that oxidative stress-induced DNA damage is difficult to repair. Taken together, this study contributes to a deeper understanding of the specific molecular mechanisms underlying CALR-mutated MPNs.

Outcomes and Patterns of Evolution of Patients with Hematological Malignancies during the COVID-19 Pandemic: A Nationwide Study (2020-2022).

Background: Early reports suggest that hematological malignancy (HM) is a relevant risk factor for morbidity and mortality in COVID-19. We investigated the characteristics, outcomes, and risk factors for mortality in patients hospitalized with HM and COVID-19. Methods: We conducted a retrospective, nationwide study using data from hospitalized patients that were provided by the Spanish Ministry of Health including all patients admitted to a Spanish hospital from 2020 to 2022 with a COVID-19 diagnosis. A descriptive analysis and correlational analyses were conducted. Logistic regression was used to assess mortality in these patients and to calculate odds ratios (ORs). Results: We collected data on 1.2 million patients with COVID-19, including 34,962 patients with HMs. The incidence of hospitalization for patients with HMs was 5.8%, and the overall mortality rate was higher than for patients without HMs (19.8% versus 12.7%, p = 0.001). Mortality rates were higher for patients with lymphomas, multiple myelomas, and leukemias than for those with myeloproliferative disorders. Having HMs was a risk factor for mortality, with OR = 1.7 (95% CI 1.66-1.75, p = 0.001). By subtype, non-Hodgkin lymphomas were the highest risk factor for mortality (OR = 1.7), followed by leukemias (OR = 1.6), Hodgkin lymphomas (OR = 1.58), and plasma cell dyscrasias (OR = 1.24). Conclusions: This study identifies the different clinical profiles of patients with HMs who are at a high risk for mortality when hospitalized with COVID-19. As members of a vulnerable population, these patients deserve special prophylactic and therapeutic measures to minimize the effects of SARS-CoV-2 infection.

Unmasking Essential Thrombocythemia: Myocardial Infarction as a Rare Complication in a Young Patient

Essential thrombocythemia (ET) is a rare myeloproliferative disorder characterized by elevated platelet counts and seldom presents with myocardial infarction (MI), particularly in younger individuals without traditional cardiovascular risk factors. We report the case of a 41-year-old woman with no significant medical history who presented with acute chest pain and elevated troponin levels. Her laboratory results indicated a markedly high platelet count, and coronary angiography revealed thrombotic stenosis in the proximal left anterior descending artery. Diagnosis of ET was confirmed by JAK2-V617F mutation and bone marrow biopsy. The patient was initially treated with hydroxyurea to reduce platelet levels, allowing for successful angioplasty three weeks later. This case highlights the importance of considering ET in the differential diagnosis of MI, especially in younger patients without other risk factors, and underscores the need for tailored management and close monitoring in such rare presentations.

Multi-Walled Carbon Nanotubes Accelerate Leukaemia Development in a Mouse Model.

Inflammation is associated with an increased risk of developing various cancers in both animals and humans, primarily solid tumors but also myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). Multi-walled carbon nanotubes (MWCNTs), a type of carbon nanotubes (CNTs) increasingly used in medical research and other fields, are leading to a rising human exposure. Our study demonstrated that exposing mice to MWCNTs accelerated the progression of spontaneous MOL4070LTR virus-induced leukemia. Additionally, similar exposures elevated pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α and induced reactive oxygen species (ROS) in a murine macrophage cell line. These effects were significantly reduced in immunodeficient mice and when mice were treated with methoxypolyethylene glycol amine (PEG)-modified MWCNTs. These findings underscore the necessity of evaluating the safety of MWCNTs, particularly for those with hematologic cancers.

Screening for Janus kinase-2 exon 12 mutations among Janus kinase-2 V617F-negative polycythemia vera suspected Iraqi patients

Abstract: BACKGROUND: Diagnosis of myeloproliferative neoplasms including polycythemia vera (PV) has been greatly improved following the identification of driver mutations at exon 12 and exon 14 of the Janus Kinase 2 (JAK2) gene. There are limited academic studies that report the frequency of the JAK2 exon 12 gene with limited number of patients. OBJECTIVES: The aim of this study was to evaluate the frequency of JAK2 exon 12 mutations among JAK2V617F-negative PV-suspected Iraqi patients. PATIENTS’, MATERIALS AND METHODS: This is a retrospective study conducted at the National Center of Hematology/Mustansiriyah University from December 2019 to January 2022; patients with suspicion of PV were enrolled in this study. Screening for JAK2 exon 14 (JAK2V617F) mutations was done for all 323 patients. Out of them, there were 102 patients with JAK2V617F-negative who retrospectively screened for JAK2 exon 12 mutations by direct sequencing (Sanger sequencing). RESULTS: Initial evaluation for the total 323 patients suspected with PV revealed that 84 cases were mutated for the JAK2V617F gene, and 239 were unmutated. The frequency of JAK2 exon 12 was about 1% among JAK2V17F-negative patients. The median age for all patients was 35 years. Among the total cases, 21 cases (20.59%) showed splenomegaly at the time of clinical onset sequencing of these cases revealed only one case mutated with JAK2 exon 12 (E543-D544del). CONCLUSION: The current study showed that the frequency of JAK2 exon 12 mutations in JAK2V617F-negative cases was very low. Despite PV patients with JAK2 exon 12 mutations represent a small proportion of total PV cases, JAK2 exon 12 mutations should be routinely screened in JAK2V617F-negative cases.

Unraveling the impact of lysosomal dysfunction on myeloproliferative neoplasm.

Lysosomal dysfunction (LD) impacts cytokine regulation, inflammation, and immune responses, influencing the development and progression of cancer. Inflammation is implicated in the pathogenesis of myeloproliferative neoplasm (MPN). With a hypothesis that LD significantly contributes to MPN carcinogenesis by inducing abnormal inflammation, our objective was to elucidate the pathophysiological mechanisms of MPN arising from an LD background. Genotyping of the LD background was performed in a cohort of MPN patients (n = 190) and healthy controls (n = 461). Logistic regression modeling, utilizing genotype data, was employed to estimate the correlation between LD and MPN. Whole transcriptome sequencing (WTS) (LD carriers = 8, non-carriers = 6) and single-cell RNA sequencing data (LD carriers = 2, non-carriers = 2, healthy controls = 2) were generated and analyzed. A higher variant frequency of LD was observed in MPN compared to healthy controls (healthy, 4.9%; MPN, 7.8%), with the highest frequency seen in polycythemia vera (PV) (odds ratio = 2.33, p = 0.03). WTS revealed that LD carriers exhibited upregulated inflammatory cytokine ligand-receptor genes, pathways, and network modules in MPNs compared to non-carriers. At the single-cell level, there was monocyte expansion and elevation of cytokine ligand-receptor interactions, inflammatory transcription factors, and network modules centered on monocytes. Notably, Oncostatin-M (OSM) consistently emerged as a candidate molecule involved in the pathogenesis of LD-related PV. In summary, an LD background is prevalent in MPN patients and leads to increased cytokine dysregulation and inflammation. OSM, as one of the potential molecules, plays a crucial role in PV pathogenesis by impairing lysosomal function.

Decoding Endothelial MPL and JAK2V617F Mutation: Insight Into Cardiovascular Dysfunction in Myeloproliferative Neoplasms.

Patients with JAK2V617F-positive myeloproliferative neoplasms (MPNs) and clonal hematopoiesis of indeterminate potential face a significantly elevated risk of cardiovascular diseases. Endothelial cells carrying the JAK2V617F mutation have been detected in many patients with MPN. In this study, we investigated the molecular basis for the high incidence of cardiovascular complications in patients with MPN. We investigated the impact of endothelial JAK2V617F mutation on cardiovascular disease development using both transgenic murine models and MPN patient-derived induced pluripotent stem cell lines. Our investigations revealed that JAK2V617F mutant endothelial cells promote cardiovascular diseases under stress, which is associated with endothelial-to-mesenchymal transition and endothelial dysfunction. Importantly, we discovered that inhibiting the endothelial TPO (thrombopoietin) receptor MPL (myeloproliferative leukemia virus oncogene) suppressed JAK2V617F-induced endothelial-to-mesenchymal transition and prevented cardiovascular dysfunction caused by mutant endothelial cells. Notably, the endothelial MPL receptor is not essential for the normal physiological regulation of blood cell counts and cardiac function. JAK2V617F mutant endothelial cells play a critical role in the development of cardiovascular diseases in JAK2V617F-positive MPNs, and endothelial MPL could be a promising therapeutic target for preventing or ameliorating cardiovascular complications in these patients.

Immune-dysregulation harnessing in myeloid neoplasms.

Myeloid malignancies arise in bone marrow microenvironments and shape these microenvironments in favor of malignant development. Immune suppression is one of the most important stages in myeloid leukemia progression. Leukemic clone expansion and immune dysregulation occur simultaneously in bone marrow microenvironments. Complex interactions emerge between normal immune system elements and leukemic clones in the bone marrow. In recent years, researchers have identified several of these pathological interactions. For instance, recent works shows that the secretion of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), from bone marrow stromal cells contributes to immune dysregulation and the selective proliferation of JAK2V617F+ clones in myeloproliferative neoplasms. Moreover, inflammasome activation and sterile inflammation result in inflamed microenvironments and the development of myelodysplastic syndromes. Additional immune dysregulations, such as exhaustion of T and NK cells, an increase in regulatory T cells, and impairments in antigen presentation are common findings in myeloid malignancies. In this review, we discuss the role of altered bone marrow microenvironments in the induction of immune dysregulations that accompany myeloid malignancies. We also consider both current and novel therapeutic strategies to restore normal immune system function in the context of myeloid malignancies.

1683P Self-care confidence as a predictor of symptom burden and quality of life in people living with myeloproliferative neoplasms

1683P Self-care confidence as a predictor of symptom burden and quality of life in people living with myeloproliferative neoplasms

Janus kinase 2 mutation-negative polycythemia-associated retinal changes in otherwise asymptomatic patients

Purpose: The purpose of this study was to document secondary polycythemia (SP)-associated retinal changes and the favorable role of phlebotomy in the treatment of SP-induced retinal complications. Design: This was a retrospective, observational, noncomparative case series. Participants: A total of 8 eyes of 4 male patients with an age range of 28–78 years were studied. Materials and Methods: A total of 04 consecutive patients were received over a year on an outpatient basis at a single tertiary care center, with only vision-related complaints. After documentation of ocular findings, all the patients were subjected to meticulous clinical and laboratory evaluation to determine the cause of ocular conditions. Patients were subjected to the treatment for underlying pathological conditions based on the outcomes of their clinical and laboratory evaluation. Main Outcome Measures: Determination of Janus kinase 2 (JAK2) mutation-negative SP as a cause of associated retinal complications and favorable role of phlebotomy as a treatment measure. Results: All the patients were adult, nonsmoker, and nonalcoholic males. A total of 05 eyes were diagnosed with proliferative vitreoretinopathy while 2 eyes had retinal venous occlusion. One eye was normal. Except SP, no other cause for retinal lesions could be ascertained in all patients. Three patients underwent phlebotomy as decided by the hematologists. Each patient was followed monthly for 6 months. All the patients showed resolution of retinal lesions at the end of follow-up. Conclusion: Nonpolycythemia vera (PV) erythrocytosis or unmutated JAK2 SP is still a very poorly studied entity. Almost no information is available regarding ocular involvement and its treatment in SP. Our observations suggest that SP may run a chronic course causing serious retinal damage such as other myeloproliferative disorders or PV and that phlebotomy has an important role in the management of such cases.

Impaired fibrinolysis in JAK2V617F-related myeloproliferative neoplasms

BackgroundMyeloproliferative neoplasms (MPNs) are characterized by a high rate of thrombotic complications that contribute to morbidity and mortality. MPN-related thrombogenesis is assumed to be multifactorial, involving both procoagulant and proinflammatory processes. Whether impaired fibrinolysis also participates in the prothrombotic phenotype of MPN has been poorly investigated. ObjectivesWe determined whether MPN, particularly JAK2V617F-positive MPN, is associated with fibrinolytic changes. MethodsTissue-type plasminogen activator (tPA)–mediated fibrinolysis was evaluated both in whole blood and plasma from mice with a hematopoietic-restricted Jak2V617F expression compared with wild-type (WT) mice (Jak2WT) using (1) halo clot lysis, (2) front lysis, and (3) plasmin generation assays. tPA clot lysis assay was performed in the plasma from 65 MPN patients (JAK2V617F mutation, n = 50; CALR mutations, n = 9) compared with 28 healthy controls. ResultsIn whole blood from Jak2V617F mice, we observed a decreased fibrinolysis characterized by a significantly lower halo clot lysis rate compared with Jak2WT (95 ± 22 vs 147 ± 39 AU/min; P < .05). Similar results were observed in plasma (halo clot lysis rate, 130 ± 27 vs 186 ± 29 AU/min; front lysis rate, 2.8 ± 1.6 vs 6.1 ± 1.2 μm.min−1; P < .05). Plasmin generation was significantly decreased both in plasma clots and standardized fibrin clots from Jak2V617F mice compared with Jak2WT mice. Among MPN patients, impaired tPA-related fibrinolysis with prolonged clot lysis time was observed in JAK2V617F and CALR patients. Plasminogen activator inhibitor-1 and α2-antiplasmin were significantly increased in plasma from JAK2V617F patients compared with controls. ConclusionOur results suggest that impaired tPA-mediated fibrinolysis represents an important prothrombotic mechanism in MPN patients that requires confirmation in larger studies.

MPN-608 Next-Generation Sequencing (NGS) Profiling and Cytogenetic Analysis for Patients With Ph-negative Myeloproliferative Neoplasms

MPN-608 Next-Generation Sequencing (NGS) Profiling and Cytogenetic Analysis for Patients With Ph-negative Myeloproliferative Neoplasms

Response, complications and risk of leukemic transformation of phosphorus-32 p treatment in philadelphia-negative chronic myeloproliferative syndromes

ObjectiveDescribe our experience in treatment with Phosphorus-32 P for refractory Philadelphia negative chronic myeloproliferative syndromes or with side effects to the usual treatment, its complications and risk of leukemic transformation. Material and methodsRetrospective descriptive study including 17 patients with a diagnosis of Philadelphia-negative chronic myeloproliferative syndrome treated with Phosphorus-32 P in our hospital from January 1985 to March 2017. Indications, response to treatment, as well as early and late complications have been analyzed. ResultsOf the 17 patients treated with 32 P (11 men, 6 women; mean age 79,8 years), 6 patients had Polycythemia Vera and 11 Essential Thrombocytosis. A single dose was administered in 9 of the subjects, the rest required two or more doses due to inadequate hematological response and/or relapse. The total dose range of Phosphorus-32 P administered was 116-951 MBq (median: 236 MBq). In 14 patients treated with Phosphorus-32 P, complete or partial response was achieved in hematimetry. In 11 patients, the response was complete, established as a platelet count < 400.000/mm3 in those diagnosed with Essential Thrombocythemia and a hematocrit < 45% in cases of Polycythemia Vera. The median follow-up of patients from the date of the first treatment of Phosphorus-32 P until study completion or death was 37 months (range: 5 - 230 months). Regarding early complications, 2 cases of anemia requiring blood transfusion were observed, and 1 case of mild thrombocytopenia. No leukemic transformation was identified. ConclusionsIn our experience, treatment with Phosphorus-32 P has been a useful therapeutic option in Philadelphia-negative chronic myeloproliferative syndromes in elderly patients who showed poor tolerance and/or resistance to first-line treatment. No leukemic transformation was identified.

Splenectomy unveils thrombocytosis in underlying myeloproliferative neoplasms with extrahepatic portal vein obstruction.

Extrahepatic portal vein obstruction (EHPVO) is a rare disease with myeloproliferative neoplasm (MPN) as the most common cause. We report that hypersplenic hematologic changes in EHPVO might be eliminated by MPN. Through experience with splenectomy for variceal control with EHPVO, we suspected that spleen might mask MPN-induced thrombocytosis, and that MPN might have a significant influence on excessive thrombocytosis after splenectomy. To clarify the influence of MPN and spleen on platelet trends, we conducted a retrospective hospital database analysis, evaluating 8 EHPVO patients with splenectomy (2 males, 6 females; from 17 years to 64 years, mean 38.3 years). Three (37.5%) of 8 were diagnosed as MPN by JAK2V617F mutation. The perioperative serum platelet counts in EHPVO without MPN were 10.5, 35.4, and 36.6 (x104/μL) preoperatively, after 1 week and 3 weeks, respectively. The platelet counts in EHPVO with MPN were 34.2, 86.4, and 137.0 (x104/μL), respectively. Splenectomy and MPN showed positive interaction on platelet increasing with statistical significance. We also examined the spleen volume index (SpVI: splenic volume (cm3) / body surface area (m2) and postoperative platelet elevations ratio (PER: 3-week postoperative platelet counts / preoperative platelet counts). However, both SpVI and PER showed no significant difference with or without MPN. Histological examination revealed splenic congestion in all 8 EHPVO cases, and splenic extramedullary hematopoiesis in 2 of 3 MPN. In EHPVO with MPN, hypersplenism causes feigned normalization of platelet count by masking MPN-induced thrombocytosis; however, splenectomy unveils postoperative thrombocytosis. Spleen in EHPVO with MPN also participates in extramedullary hematopoiesis.

Hereditary hemochromatosis as an independent predictor of portal vein thrombosis: national inpatient sample (2016-2020) analysis

Hereditary hemochromatosis is a common inherited metabolic disorder of iron metabolism with variable penetrance. Portal vein thrombosis has several well-known causes including cirrhosis, myeloproliferative neoplasm, inflammatory conditions of the abdomen, intra-abdominal malignancy, intra-abdominal surgery, and thrombophilia. It is unknown whether hereditary hemochromatosis is associated with portal vein thrombosis. Material and methodology. A retrospective analysis of the National Inpatient Sample database from 2016 to 2020 was conducted using International Classification of Diseases-10 codes to identify hospitalizations with portal vein thrombosis. We used multivariate regression analysis to calculate the adjusted odds ratio after controlling for age, gender, insurance type, Charlson Comorbidity Index, cirrhosis, myeloproliferative neoplasm, inflammatory conditions of the abdomen, intra-abdominal malignancy, intra-abdominal surgery, history of past thrombosis, thrombophilia, end-stage renal disease, obesity,smoking, and hyperlipidemia. Results. There were 25805 hospitalizations with primary diagnosis of portal vein thrombosis. Multivariate logistic regression showed that hereditary hemochromatosis was independently associated with portal vein thrombosis (Odds ratio= 4.7, 95% CI=1.15 to 19.35, p-value=0.03) when cirrhosis, myeloproliferative neoplasm, inflammatory conditions of the abdomen, intra-abdominal malignancy, history of thrombosis, history of abdominal surgery, history of thrombophilia, and end-stage renal disease among other factors were controlled.

Combination of ligand‑based and structure‑based virtual screening for the discovery of novel Janus kinase 2 inhibitors against philadelphia-negative myeloproliferative neoplasms.

The activating V617F mutation in Janus kinase 2 (JAK2) has been shown to be the major cause for classic Philadelphia-negative myeloproliferative neoplasms (MPNs). Thus, the development of pharmacologic JAK2 inhibitors is an essential move in combating MPNs. In this study, screening methods examining both ligands and their structures were developed to discover novel JAK2 inhibitors from the ChemDiv database with virtual screening identifying 886 candidate inhibitors. Next, these compounds were further filtered using ADMET, drug likeliness, and PAINS filtering, which reduced the compound number even further. This consolidated list of candidate compounds (n = 49) was then evaluated biologically at molecular level and the highest performing inhibitor with a novel scaffold was selected for further examination. This candidate inhibitor, CD4, was then subjected to molecular dynamics studies, with complex stability, root-mean-square deviation, radius of gyration, binding free energy, and binding properties all examined. The result suggested that CD4 interacts with JAK2 and that the CD4-JAK2 complex is stable. This study was able to identify a candidate inhibitor that warrants further examination and optimization and may potentially serve as a future MPN treatment.