Article
Multidisciplinary Sciences
Yusuke Kimishima, Tomofumi Misaka, Tetsuro Yokokawa, Kento Wada, Koki Ueda, Koichi Sugimoto, Keiji Minakawa, Kazuhiko Nakazato, Takafumi Ishida, Motohiko Oshima, Shuhei Koide, Kotaro Shide, Kazuya Shimoda, Atsushi Iwama, Kazuhiko Ikeda, Yasuchika Takeishi
Summary: The study demonstrates that clonal hematopoiesis with JAK2V617F exacerbates PH by promoting the accumulation of neutrophils in pulmonary arterial regions, ultimately leading to pulmonary arterial remodeling and increased disease severity.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Paola Guglielmelli, Giuseppe G. Loscocco, Carmela Mannarelli, Elena Rossi, Francesco Mannelli, Francesco Ramundo, Giacomo Coltro, Silvia Betti, Chiara Maccari, Sara Ceglie, Patrizia Chiusolo, Chiara Paoli, Tiziano Barbui, Ayalew Tefferi, Valerio De Stefano, Alessandro M. Vannucchi
Summary: The study analyzed the impact of JAK2V617F VAF on thrombosis in PV patients, finding that VAF > 50% is an independent strong predictor of future VT, but not associated with AT. The results suggest that AT and VT may require distinct management strategies.
BLOOD CANCER JOURNAL
(2021)
Article
Medicine, General & Internal
Cengiz Ceylan, Berk Ozyilmaz, Ozgur Kirbiyik, Mehmet Can Ugur, Ozge Ozer
Summary: This study found that ET patients with CALR mutation had higher platelet count and blood LDH levels, while those with JAK2 mutation had higher blood haemoglobin levels. Additionally, the PCT level was higher in the CALR group compared to other patient groups.
INTERNATIONAL JOURNAL OF CLINICAL PRACTICE
(2021)
Article
Hematology
Graciela Rabadan Moraes, Florence Pasquier, Christophe Marzac, Eric Deconinck, Carlotta Caterina Damanti, Gwendoline Leroy, Mira El-Khoury, Wassim El Nemer, Jean-Jacques Kiladjian, Hana Raslova, Albert Najman, William Vainchenker, Caroline Marty, Christine Bellanne-Chantelot, Isabelle Plo
Summary: This study identified an EPOR variant in a large family with JAK2-positive MPN, indicating the importance of inherited-risk alleles affecting the JAK2/STAT pathway in MPN. The findings suggest potential implications for risk assessment and treatment of MPN.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anders L. Sorensen, Hans C. Hasselbalch, Mads Emil Bjorn, Claus H. Nielsen, Sabrina Cordua, Vibe Skov, Lasse Kjaer, Henrik E. Poulsen, Christina Ellervik
Summary: The study suggests a potential association between somatic mutations in MPNs and oxidative stress, with higher levels of oxidative stress markers in mutation-positive individuals. Impaired mitochondrial antioxidative defense may contribute to the development of mutations associated with MPNs.
Article
Biotechnology & Applied Microbiology
Jie Zhou, Hao Wu, Cheng Guo, Bing Li, Li-Li Zhou, Ai-Bin Liang, Jian-Fei Fu
Summary: The study identified the expression and regulation patterns of lncRNAs in JAK2V617F-positive cMPNs, along with potential carcinogenic factors and signaling pathways related to dysregulated lncRNAs and important genes. Further investigation is warranted to explore the role of these factors in the pathogenesis of cMPNs.
Article
Cell Biology
Kengo Takeda, Kenji Tago, Megumi Funakoshi-Tago
Summary: The point mutation (V617F) in the JAK2 gene promotes the expression of DDX5, which contributes to the development of MPN through the activation of STAT5. Inhibition of DDX5 suppresses mTOR activation, cell proliferation, and tumor growth in a mouse model of MPN.
CELLULAR SIGNALLING
(2023)
Article
Hematology
Samah Alimam, William Villiers, Richard Dillon, Michael Simpson, Manohursingh Runglall, Alexander Smith, Prodromos Chatzikyriakou, Paul Lavender, Anju Kanda, Ken Mills, Beatriz Bellosillo Paricio, James Kaufman-Cook, Sophie Ord, Shahram Kordasti, Deepti Radia, Claire Woodley, Yvonne Francis, Ghulam Mufti, Donal P. McLornan, Claire N. Harrison
Summary: The study identified similar patterns of gene expression and DNA methylation in patients with essential thrombocythemia (ET) with known driver mutations and those with triple-negative disease, suggesting that the ET phenotype may be primarily driven by transcriptional misregulation and may propagate downstream via MAPK, tumor necrosis factor, and NF kappa B pathways. These findings highlight potential novel mechanisms of disease initiation that require further evaluation.
Article
Oncology
Antonio Bruno Alves-Silva, Bruna Alves Fenerich, Natasha Peixoto Fonseca, Jaqueline Cristina Fernandes, Juan Luiz Coelho-Silva, Diego Antonio Pereira-Martins, Thiago Mantello Bianco, Priscila Santos Scheucher, Eduardo Magalhaes Rego, Fernando Chahud, Joao Agostinho Machado-Neto, Lorena Lobo Figueiredo-Pontes, Fabiola Traina
Summary: This study investigated the effects of phenformin on Jak2(V617F)-knockin MPN mice. The results showed that phenformin increased the percentages of LSK, MP, and MPP populations in the bone marrow, but did not reduce the disease burden. Further studies are needed to understand the effects of phenformin on early hematopoietic progenitors.
INVESTIGATIONAL NEW DRUGS
(2022)
Review
Microbiology
Christina Schjellerup Eickhardt-Dalboge, Anna Cacilia Ingham, Henrik V. Nielsen, Kurt Fuursted, Christen Rune Stensvold, Lee O'Brien Andersen, Morten Kranker Larsen, Lasse Kjaer, Sarah Friis Christensen, Trine Alma Knudsen, Vibe Skov, Christina Ellervik, Lars Ronn Olsen, Hans Carl Hasselbalch, Jens Jorgen Elmer Christensen, Xiaohui Chen Nielsen
Summary: This study investigates the gut microbiota in patients with essential thrombocythemia (ET) and found that they have higher richness and different bacterial composition compared to healthy controls. The relative abundance of certain bacteria within the Firmicutes phylum is lower in ET patients, including an important immunoregulative bacterium Faecalibacterium. These findings suggest a potential role of gut microbiota in immune dysregulation of ET patients.
MICROBIOLOGY SPECTRUM
(2023)
Article
Hematology
Alison R. Moliterno, Hannah Kaizer, Brandi N. Reeves
Summary: Polycythemia vera (PV) is a hematopoietic stem cell neoplasm characterized by overproduction of red blood cells, platelets, and neutrophils due to activating somatic mutations in the JAK2 gene. This disease is associated with significant burden of symptoms, high rates of vascular events, and progression to myelofibrosis phase or acute leukemia. The JAK2(V617F) variant allele frequency (VAF) plays a crucial role in the pathogenesis, diagnosis, prognosis, and treatment of PV.
Article
Immunology
Amanda Fernandes de Oliveira Costa, Leticia Olops Marani, Thiago Mantello Bianco, Adriana Queiroz Arantes, Izabela Aparecida Lopes, Diego Antonio Pereira-Martins, Leonardo Carvalho Palma, Priscila Santos Scheucher, Josiane Lilian dos Santos Schiavinato, Larissa Sarri Binelli, Cleide Araujo Silva, Susumu S. Kobayashi, Joao Agostinho Machado-Neto, Eduardo Magalhaes Rego, Robert Samuel Welner, Lorena Lobo de Figueiredo-Pontes
Summary: NK cells play a role in eliminating tumor cells through direct cytolytic activity and promoting antitumor immune response. This study suggests that NK cells in myeloproliferative neoplasms (MPN) have an immature phenotype and deficient cytotoxicity, which may lead to impaired tumor surveillance.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Christina Schjellerup Eickhardt-Dalbge, Anna Cacilia Ingham, Henrik V. Nielsen, Kurt Fuursted, Christen Rune Stensvold, Lee O'Brien Andersen, Morten Kranker Larsen, Lasse Kjaer, Sarah Friis Christensen, Trine Alma Knudsen, Vibe Skov, Christina Ellervik, Lars Rnn Olsen, Hans Carl Hasselbalch, Jens Jrgen Elmer Christensen, Xiaohui Chen Nielsen
Summary: Essential thrombocythemia (ET) is a type of leukemia characterized by excessive platelet production. Inflammation has been shown to play a vital role in the initiation and progression of other myeloproliferative neoplasms, and the gut microbiota is known to be important in immune system regulation. However, the gut microbiota of ET patients has not been investigated. In this study, we compared the gut microbiota of ET patients with healthy controls, providing new insights into this field. We found significant differences in the gut microbiota of ET patients compared to healthy controls, with ET patients having a lower relative abundance of important immunoregulative bacteria. Furthermore, we observed pronounced gut microbiota signatures in ET patients with the JAK2V617F mutation, confirming the importance of the underlying mutation, immune response, and microbiota composition.
MICROBIOLOGY SPECTRUM
(2023)
Article
Oncology
Daisuke Shinoda, Yaeko Nakajima-Takagi, Motohiko Oshima, Shuhei Koide, Kazumasa Aoyama, Atsunori Saraya, Hironori Harada, Bahityar Rahmutulla, Atsushi Kaneda, Kiyoshi Yamaguchi, Yoichi Furukawa, Haruhiko Koseki, Kazuya Shimoda, Tomoaki Tanaka, Goro Sashida, Atsushi Iwama
Summary: The insufficiency of PRC1.1, a component of polycomb repressive complex 1, promotes the development of myelofibrosis and acts as a tumor suppressor in this process. This impact is distinct from the effect of PRC2 insufficiency on the pathogenesis of myelofibrosis.
Article
Oncology
Jie Zhou, Cheng Guo, Hao Wu, Bing Li, Li-Li Zhou, Ai-Bin Liang, Jian-Fei Fu
Summary: In Jak2(V617F) positive samples, Dnmt3a is downregulated due to the binding of Stat5a with the Dnmt3a promoter, affecting cell proliferation and cycle distribution. The specific site where Stat5a binds is the GAS motif at the Dnmt3a promoter. Dnmt3a induces G0/G1 arrest through regulating the miR-17-5p/Cdkn1a axis, providing a potential treatment target for cMPNs.