Editorial Material
Oncology
Rupali R. Bhave, Ruben Mesa, Michael R. Grunwald
Summary: The rapid pace of drug development in hematology has led to multiple approvals for myelofibrosis (MF) and polycythemia vera (PV) in recent years. There are also many innovative agents and combinations being explored for myeloproliferative neoplasms (MPNs). In the past year, there have been advances in MF, PV, and essential thrombocythemia, focusing on strategies to optimize inhibition of signal transduction, modify epigenetics, enhance apoptosis, target DNA replication, transform host immunity, and alter the tumor microenvironment. The increased focus on MPNs brings hope for improving morbidity and mortality in this group of diseases.
Article
Oncology
Judith Gecht, Ioannis Tsoukakis, Kim Kricheldorf, Frank Stegelmann, Martine Klausmann, Martin Griesshammer, Holger Schulz, Wiebke Hollburg, Joachim R. Goethert, Katja Sockel, Florian H. Heidel, Norbert Gattermann, Christoph Maintz, Haifa K. Al-Ali, Uwe Platzbecker, Richard Hansen, Mathias Haenel, Stefani Parmentier, Martin Bommer, Heike L. Pahl, Fabian Lang, Martin Kirschner, Susanne Isfort, Tim H. Bruemmendorf, Konstanze Doehner, Steffen Koschmieder
Summary: In patients with myeloproliferative neoplasms (MPN) and kidney dysfunction, a higher rate of thrombosis is reported, with specific risk factors including arterial hypertension, MPN treatment, and increased inflammation for kidney dysfunction, and arterial hypertension, non-excessive platelet counts, and antithrombotic therapy for thrombosis. Risk factors varied between MPN subtypes, suggesting an increased risk of thrombosis in MPN patients with kidney dysfunction, mandating closer monitoring and possibly early thromboprophylaxis._overlap in disease-specific attributes indicates common mechanisms in MPN pathogenesis, kidney dysfunction, and thrombosis.
Review
Medicine, General & Internal
Abdulrahman F. Al-Mashdali, Mahmood B. Aldapt, Alaa Rahhal, Yousef M. Hailan, Israa Elhakeem, Elrazi A. Ali, Waail Rozi, Mohamed A. Yassin
Summary: Philadelphia-negative myeloproliferative neoplasms (MPNs) are rarely diagnosed in pediatrics, leading to limited knowledge about their clinical presentation, mutational status, and complications. This study reviewed the literature and found that pediatric MPNs have different clinical characteristics, vascular and long-term complications, types of driver mutations, and treatment approaches compared to adults.
Article
Multidisciplinary Sciences
Mattheus H. E. Wildschut, Julien Mena, Cyril Dordelmann, Marc van Oostrum, Benjamin D. Hale, Jens Settelmeier, Yasmin Festl, Veronika Lysenko, Patrick M. Schurch, Alexander Ring, Yannik Severin, Michael S. Bader, Patrick G. A. Pedrioli, Sandra Goetze, Audrey van Drogen, Stefan Balabanov, Radek C. Skoda, Massimo Lopes, Bernd Wollscheid, Alexandre P. A. Theocharides, Berend Snijder
Summary: In this study, we integrated ex vivo drug response and proteotype analyses to discover targetable vulnerabilities and associated therapeutic strategies for myelofibrosis patients. We identified three targetable vulnerabilities, including the sensitivity to BET and HDAC inhibitors driven by CALR mutations, the sensitivity to drugs targeting pro-survival signaling and DNA replication associated with an MCM complex-high proliferative signature, and the ER stress response in homozygous CALR mutations. Our findings provide a molecularly motivated roadmap for individualized treatment of myelofibrosis patients.
NATURE COMMUNICATIONS
(2023)
Article
Hematology
Laura Herbreteau, Francis Couturaud, Clement Hoffmann, Luc Bressollette, Brigitte Pan-Petesch, Laetitia Rio, Eric Lippert, Jean-Christophe Ianotto
Summary: Myeloproliferative neoplasms (MPNs) patients with atrial fibrillation (AF) and/or peripheral arterial disease (PAD) have a higher incidence of thrombotic and hemorrhagic events.
THROMBOSIS RESEARCH
(2023)
Review
Oncology
Sylvie Hermouet
Summary: Knowledge on the myeloproliferative neoplasms (MPNs) – polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) – including the mutations associated with MPNs and its lack of disease specificity, as well as the role of mutations in inflammation, have been extensively studied. Various drugs have been tested in MPNs, but they remain incurable diseases. This review aims to present current knowledge on the pathogenic mechanisms associated with PV, ET or PMF to develop novel, curative therapies.
FRONTIERS IN ONCOLOGY
(2023)
Review
Medicine, General & Internal
Joan How, Charlotte Story, Jean Marie Connors
Summary: Myeloproliferative neoplasms (MPNs) are stem cell clonal neoplasms characterized by expansion of late myeloid cells, with elevated thrombosis risk contributing significantly to morbidity and mortality. While current consensus guidelines lack specific recommendations for anticoagulant choice in treating venous thromboembolism (VTE) in MPNs, the increasing use of direct oral anticoagulants (DOACs) in cancer-associated VTE treatment is based on new evidence, though limited data is available for MPNs specifically. Further research is needed to evaluate the safety and efficacy of DOACs in MPNs.
POSTGRADUATE MEDICINE
(2021)
Review
Oncology
Rory M. Shallis, Nikolai A. Podoltsev
Summary: Both PV and ET are driven by JAK-STAT pathway activation, leading to recent research focusing on inhibiting this pathway to improve management and outcomes. New agents exploiting a growing understanding of PV and ET pathogenesis and disease evolution mechanisms are being developed, with potential to modify disease course and show clinical efficacy in patients.
BIOMARKER RESEARCH
(2021)
Article
Hematology
Christophe Nicol, Nadine Ajzenberg, Karine Lacut, Francis Couturaud, Eric Lippert, Brigitte Pan-Petesch, Jean-Christophe Ianotto
Summary: The incidence and risk factors of bleedings in patients with myeloproliferative neoplasms (MPNs) have been studied. Risk factors include abnormal white blood cell and platelet counts, history of bleeding, secondary hematological disorders, and secondary cancers.
THROMBOSIS AND HAEMOSTASIS
(2022)
Review
Oncology
Carl C. Crodel, Kathleen Jentsch-Ullrich, Marcel Reiser, Lutz Jacobasch, Annette Sauer, Hans Tesch, Thomas Ulshoefer, Regine Wunschel, Francesca Palandri, Florian H. Heidel
Summary: Patients with polycythemia vera (PV) have an increased risk of thromboembolic events compared to healthy individuals, mainly due to factors such as elevated hematocrit, JAK2 driver mutation, and cardiovascular risk factors. The study emphasizes the variability in cytoreductive treatment in real-life settings, with age and history of thromboembolic events being key risk factors for high-risk PV patients.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Derek W. Brown, Weiyin Zhou, Youjin Wang, Kristine Jones, Wen Luo, Casey Dagnall, Kedest Teshome, Alyssa Klein, Tongwu Zhang, Shu-Hong Lin, Olivia W. Lee, Sairah Khan, Jacqueline B. Vo, Amy Hutchinson, Jia Liu, Jiahui Wang, Bin Zhu, Belynda Hicks, Andrew St Martin, Stephen R. Spellman, Tao Wang, H. Joachim Deeg, Vikas Gupta, Stephanie J. Lee, Neal D. Freedman, Meredith Yeager, Stephen J. Chanock, Sharon A. Savage, Wael Saber, Shahinaz M. Gadalla, Mitchell J. Machiela
Summary: The study identified 6 germline susceptibility loci and high frequencies of mosaic chromosomal alterations (mCAs) in myelofibrosis cases. The mCAs involving JAK2 were found to be strong promoters of clonal expansion in mutated clones of myelofibrosis cases.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Roelof H. Bekendam, Katya Ravid
Summary: Platelets play crucial roles in thrombosis and hemostasis. They are also involved in cancer progression and tumor invasion. Activation of platelets by cancers can contribute to metastasis and increase the risk of thrombosis. Platelet secretion provides potential biomarkers for predicting thrombotic risk and tumor progression. Myeloproliferative neoplasms (MPNs) are characterized by abnormal function and number of blood cells, leading to thrombotic and hemorrhagic complications. Mouse models with MPN phenotype have been studied for their thrombotic phenotype, showing the complexity of clotting and bleeding risk. This review focuses on platelets in cancer-associated thrombosis and MPN experimental models.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Oncology
Angela Liu, Leonard Naymagon, Douglas Tremblay
Summary: This review explores the treatment considerations of splanchnic vein thromboses (SVTs) associated with myeloproliferative neoplasms (MPNs). Anticoagulation is the mainstay of therapy, and cytoreductive therapy is recommended according to MPN treatment guidelines. Endovascular intervention may be considered in the acute setting to prevent or mitigate potential portal hypertensive complications in patients with occlusive or extensive clot burden.
Article
Oncology
Xiao-qing Li, Jia-jun Liu, Cheng-cheng Liu
Summary: This article reports a case of a PV patient with a double mutation of JAK2 gene and demonstrates the effectiveness of combination therapy with Ruxolitinib and IFN-α in reducing the burden of mutant alleles.
FRONTIERS IN ONCOLOGY
(2022)
Article
Hematology
Andrew L. Sochacki, Cosmin Adrian Bejan, Shilin Zhao, Ameet Patel, Ashwin Kishtagari, Travis P. Spaulding, Alexander J. Silver, Shannon S. Stockton, Kelly Pugh, R. Dixon Dorand, Manasa Bhatta, Nicholas Strayer, Siwei Zhang, Christina A. Snider, Thomas Stricker, Aziz Nazha, Alexander G. Bick, Yaomin Xu, Michael R. Savona
Summary: Treatment decisions in primary myelofibrosis are usually determined by various prognostic systems, but they do not routinely incorporate patient-specific comorbidities. In this study, the impact of comorbidities on survival was assessed, and it was found that specific comorbidities were associated with inferior survival in primary myelofibrosis patients. By including comorbidities in the risk evaluation, the prognostic capability of genetics-based scoring systems could be enhanced.