Review
Oncology
Alexandre Guy, Johanne Poisson, Chloe James
Summary: Thrombosis is a major complication of myeloproliferative neoplasms, with risk factors including age, thrombosis history, and various complex mechanisms involving blood cell types, plasma factors, and endothelial cells. Additional cardiovascular events may stem from arterial vasospasm. Potential promising therapeutic targets not currently focused on include neutrophil extracellular traps and vascular reactivity.
Review
Oncology
Graeme Greenfield, Mary Frances McMullin, Ken Mills
Summary: Philadelphia negative myeloproliferative neoplasms (MPN) constitute a heterogeneous group of clonal myeloid stem cell disorders, including polycythaemia vera, essential thrombocythaemia and primary myelofibrosis. These disorders are characterized by constitutive activation of the JAK/STAT signaling pathway, often with driving mutations in JAK2, CALR and MPL. Co-occurring epigenetic factors may also play a role, while prognostic implications vary depending on disease phenotype, genotype and other external factors.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Erika Morsia, Elena Torre, Antonella Poloni, Attilio Olivieri, Serena Rupoli
Summary: Despite their differences in clinical presentation, myeloproliferative neoplasms (MPN) share similarities in morphology, propensity for thrombotic events and leukemia transformation, and a complex molecular pathogenesis. Key driver mutations, such as JAK2, MPL, and CALR, activate the JAK-STAT signaling pathway, which is characteristic of MPN pathogenesis. Recent research has revealed the presence of co-occurring somatic mutations associated with epigenetic regulation, mRNA splicing, transcriptional mechanisms, signal transduction, and DNA repair mechanisms in MPN patients. Integrating genetic information into clinical practice has already improved disease monitoring and provided prognostic information regarding disease progression. While current therapeutic approaches have limited disease-modifying activity, a deeper understanding of the genetic basis of MPN has identified potential targets for targeted therapies. This review aims to explore the molecular landscape of MPN, providing a comprehensive overview of driver mutations, additional mutations, their impact on pathogenesis, prognostic value, and future implications for therapeutic management.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Alanna Barrios-Ruiz, Daniel Davila-Gonzalez, Eric Fountain, Lee Cheng, Srdan Verstovsek, Cristhiam M. Rojas-Hernandez
Summary: The study aimed to verify the concordance of ICD code-based diagnosis with true clinical diagnosis of polycythemia or erythrocytosis and found that the accuracy of ICD code-based diagnoses had limitations, leading to misidentification in a significant fraction of cases. Research based solely on ICD codes could potentially impact patient care and public health, emphasizing the need to weigh limitations when conveying research findings.
SCIENTIFIC REPORTS
(2022)
Editorial Material
Hematology
Ana Rio-Machin, Jude Fitzgibbon
Summary: In this study, Li et al and Duployez et al investigate the clinical and genetic landscape of DDX41 germline variants in patients with acute myeloid leukemia (AML). They find that AML with DDX41 germline variants represents a distinct subtype characterized by late-onset disease, normal karyotype, male sex skewing, and favorable outcome.
Editorial Material
Hematology
Heike L. Pahl
Summary: The identification of sentinel mutations in MPN patients, which significantly increase the risk of leukemic transformation, even when not present in leukemic cells, is a crucial advancement in understanding and managing the disease. These mutations act as early indicators of potential disease progression, similar to canaries in a coal mine.
Review
Biochemistry & Molecular Biology
Francisca Ferrer-Marin, Ernesto Jose Cuenca-Zamora, Pedro Jesus Guijarro-Carrillo, Raul Teruel-Montoya
Summary: In patients with chronic Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), leukocytes play a significant role in thrombosis. Neutrophils and monocytes in MPN patients show a pro-coagulant activated phenotype and release extracellular neutrophil traps (NETs) that contribute to platelet activation and coagulation mechanisms. Therapeutic strategies targeting NETs may reduce thrombotic complications in these patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Rhiannon Morris, Liesl Butler, Andrew Perkins, Nadia J. Kershaw, Jeffrey J. Babon
Summary: LNK is an adaptor protein that regulates cytokine signaling and constrains the activation of the JAK-STAT pathway. Mutations in LNK can lead to increased signaling and contribute to various hematological and inflammatory diseases.
Article
Cell Biology
Maike Buettner-Herold, Carsten Sticht, Thorsten Wiech, Stefan Porubsky
Summary: Patients with MPNs or MDS/MPNs often exhibit significant glomerular scarring in renal biopsies, indicating the importance of early recognition and control of risk factors for kidney failure.
Review
Biochemistry & Molecular Biology
Dominik Kiem, Sandro Wagner, Teresa Magnes, Alexander Egle, Richard Greil, Thomas Melchardt
Summary: Philadelphia chromosome negative myeloproliferative neoplasms consist of polycythemia vera, essential thrombocytosis, and primary myelofibrosis. Mutations in JAK2, MPL, or CALR characterize these disorders, with additional mutations leading to myeloid cell lineages expansion and marrow fibrosis in PMF. Chronic inflammation plays a significant role in the disease initiation and progression, with neutrophilic granulocytes playing a major role in the pathogenesis of thromboembolic events.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Maria Luz Morales, Francisca Ferrer-Marin
Summary: This review discusses factors other than genetic alterations that may play a role in the origin, evolution, and progression of myeloproliferative neoplasms (MPNs). It highlights the importance of exploring non-genetic mechanisms and provides a summary of studies investigating these factors. These studies focus on MPN cell-intrinsic or -extrinsic factors and their interaction through various approaches.
Article
Hematology
Jihyun Song, Soo Jin Kim, Jahnavi Gollamudi, Perumal Thiagarajan, Josef T. Prchal
Summary: Thromboses in polycythemia vera (PV) and essential thrombocythemia (ET) are not well understood. This study discovered that the absence of a transcription factor called KLF2 in neutrophils causes thrombosis, and its expression is lower in PV and ET patients compared to controls. The JAK-STAT pathway may downregulate KLF2 expression, as it is inversely correlated to JAK2V617F allelic burden. Furthermore, low KLF2 expression is associated with upregulation of thrombotic genes and increased thrombotic events. Pegylated interferon alfa can induce KLF2 expression, making it a potential therapeutic target for preventing thrombosis in PV and ET.
Article
Biochemistry & Molecular Biology
Cosimo Cumbo, Luisa Anelli, Antonella Zagaria, Nicoletta Coccaro, Francesco Tarantini, Giorgina Specchia, Pellegrino Musto, Francesco Albano
Summary: The risk of developing a solid cancer is a major concern for patients with myeloproliferative neoplasms (MPNs). There have been suggestions of various cellular and molecular mechanisms linking these two diseases, but many questions remain unanswered. This study aims to explore the biological aspects of the complex clinical scenario in MPN patients developing a second cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Yi Zhang, Qike Zhang, Qingchi Liu, Huibing Dang, Sujun Gao, Wei Wang, Hu Zhou, Yuqing Chen, Liangming Ma, Jishi Wang, Haiping Yang, Binhua Lu, Hewen Yin, Liqing Wu, Shanshan Suo, Qingwei Zhao, Hongyan Tong, Jie Jin
Summary: In this phase 2 trial, jaktinib showed promise as a treatment option for myelofibrosis patients who have become refractory to or relapsed after ruxolitinib treatment.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Oncology
Evan M. Braunstein, Hang Chen, Felicia Juarez, Fanghan Yang, Lindsay Tao, Igor Makhlin, Donna M. Williams, Shruti Chaturvedi, Aparna Pallavajjala, Theodoros Karantanos, Renan Martin, Elizabeth Wohler, Nara Sobreira, Christopher D. Gocke, Alison R. Moliterno
Summary: Familial clustering of myeloproliferative neoplasms (MPN) is well known, with increased risk among first-degree relatives, and rare germline coding variants in the ERBB2 gene are associated with an increased risk for development of MPN. The ERBB2 gene is likely to contribute to cancer risk in combination with additional risk alleles.