Article
Oncology
Jean Pegliasco, Pierre Hirsch, Christophe Marzac, Francoise Isnard, Jean-Come Meniane, Caroline Deswarte, Philippe Pellet, Celine Lemaitre, Gwendoline Leroy, Graciela Rabadan Moraes, Helene Guermouche, Barbara Schmaltz-Panneau, Florence Pasquier, Chrystelle Colas, Patrick R. Benusiglio, Odile Bera, Jean-Henri Bourhis, Eolia Brissot, Olivier Caron, Samy Chraibi, Pascale Cony-Makhoul, Christine Delaunay-Darivon, Simona Lapusan, Flore Sicre de Fontbrune, Pascal Fuseau, Albert Najman, William Vainchenker, Francois Delhommeau, Jean-Baptiste Micol, Isabelle Plo, Christine Bellanne-Chantelot
Summary: The study revealed that carriers of the 14q32 duplication displayed early clonal hematopoiesis, increasing the risk of myeloid neoplasms. Different pathways were identified in the development of the disease, with one leading to early MPN development and the other directly to AML.
Review
Medicine, General & Internal
Giovanni Fulvio, Chiara Baldini, Marta Mosca, Antonello di Paolo, Guido Bocci, Giuseppe Alberto Palumbo, Emma Cacciola, Paola Migliorini, Rossella Cacciola, Sara Galimberti
Summary: This article reviews possible mechanisms linking clonal hematopoiesis of indeterminate potential (CHIP) to chronic myeloproliferative neoplasms (MPNs), autoimmune diseases (ADs), and cardiovascular diseases (CADs). The presence of CHIP may be associated with immune reactions and thrombosis.
FRONTIERS IN MEDICINE
(2023)
Review
Medical Laboratory Technology
Xinshu Xie, Meng Su, Kehan Ren, Xuezhen Ma, Zhiyi Lv, Zhaofeng Li, Yang Mei, Peng Ji
Summary: This review summarizes the recent advances in the discovery of clonal hematopoiesis (CH) and its mutations, as well as the relationship between CH mutations and the inflammatory bone marrow microenvironment. The focus is on the most commonly mutated and well-studied genes in CH and their contributions to innate immune responses and inflammatory signaling, particularly in hematopoietic cells of the bone marrow. The review also discusses the interrelationship between the inflammatory bone marrow microenvironment and CH mutations, and provides perspectives on the challenges in the field and possible future directions to better understand the pathophysiology of CH.
TRANSLATIONAL RESEARCH
(2023)
Review
Chemistry, Medicinal
Michael Stephan Bader, Sara Christina Meyer
Summary: The discovery of the activating V617F mutation in JAK2 has greatly contributed to our understanding of myeloproliferative neoplasms (MPN). JAK2 inhibitors have become a standard treatment option for certain forms of MPN and offer significant benefits for patients. However, there are still challenges to be addressed in the targeted therapy of MPN with JAK2 inhibitors, such as reducing the MPN clone and overcoming drug resistance.
Review
Oncology
Thomas Kohnke, Ravindra Majeti
Summary: Our understanding of the relationship between clonal hematopoiesis and various health conditions has greatly expanded in recent years, with a focus on early intervention as it can indicate the onset of diseases. Despite the increase in incidental findings of clonal hematopoiesis, there is currently a lack of evidence-based management strategies. The review discusses the current state of research on clonal hematopoiesis and the challenges in developing clinical trials, highlighting the need for urgent prospective trials to address this issue.
Article
Medicine, Research & Experimental
Laneshia K. Tague, Karolyn A. Oetjen, Anirudh Mahadev, Matthew J. Walter, Hephzibah Anthony, Daniel Kreisel, Daniel C. Link, Andrew E. Gelman
Summary: Clonal hematopoiesis (CH) in DNA damage response (DDR) genes is prevalent in lung transplant recipients and is associated with posttransplant outcomes including cytomegalovirus activation and mycophenolate intolerance.
Review
Oncology
Simona Stivala, Sara C. Meyer
Summary: Somatic mutations in JAK2, calreticulin, and MPL genes drive myeloproliferative neoplasms (MPN), and recent technological advances have revealed a heterogeneous genomic landscape with additional mutations in epigenetic regulators and splicing factors. These mutations are of diagnostic and prognostic value, informing treatment decisions and guiding the development of new therapeutic options for MPN.
Letter
Oncology
Antonella Zagaria, Francesco Tarantini, Paola Orsini, Luisa Anelli, Cosimo Cumbo, Nicoletta Coccaro, Giuseppina Tota, Crescenzio Francesco Minervini, Elisa Parciante, Maria Rosa Conserva, Immacolata Redavid, Alessandra Ricco, Immacolata Attolico, Giorgina Specchia, Pellegrino Musto, Francesco Albano
Summary: This study investigated the genomic and clinical features of 80 erythrocytosis patients and found that male patients with idiopathic erythrocytosis and normal EPO levels may be the best candidates for searching for the JAK2 GGCC_46/1 haplotype and CALR rs1049481_G allele.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2022)
Review
Medicine, General & Internal
Jaskamal Padda, Khizer Khalid, Jayant Yadav, Abdulelah H. Almanie, Krutagni Adwait Mehta, Hussam Al Hennawi, Nymisha L. Boddeti, Victor Yosef Melt Campos, Gutteridge Jean-Charles
Summary: The TET2 gene, located on chromosome 4q24, has been linked to hematological malignancies. Mutations in the TET2 gene are associated with various myeloid malignancies and can lead to deregulation of hematopoiesis. Further studies are needed to better understand the role of TET2 gene mutations in different diseases and improve patient care and management.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2021)
Article
Oncology
Gajalakshmi Ramanathan, Jane H. Chen, Nitya Mehrotra, Tiffany Trieu, Aaron Huang, Eduard Mas, Jessica Monterrosa E. Mena, Bishop Bliss, David A. Herman, Michael T. Kleinman, Angela G. Fleischman
Summary: Smoking is associated with clonal hematopoiesis of indeterminate potential (CHIP) which increases the risk of hematologic malignancy and cardiovascular disease. This study showed that smoking induces an inflammatory response in the bone marrow environment, promoting clonal expansion of existing gene mutations in hematopoietic stem cells.
FRONTIERS IN ONCOLOGY
(2023)
Article
Hematology
Anna Hinze, Jenny Rinke, Carl C. Crodel, Susanne Moebius, Vivien Schaefer, Florian H. Heidel, Andreas Hochhaus, Thomas Ernst
Summary: This study genetically characterized 95 MPN patients using targeted NGS and found TET2, DNMT3A, and ASXL1 as the most common co-mutations to classical driver mutations. The study highlights JAK2(V617F) and epigenetic modifier genes as early events in hematologic disease formation.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Medicine, Research & Experimental
Huan Ge, Caolin Wang, Chaoquan Tian, Yanyan Diao, Wanqi Wang, Xiangyu Ma, Jian Zhang, Honglin Li, Zhenjiang Zhao, Lili Zhu
Summary: WWQ-131, a highly selective JAK2 inhibitor, effectively inhibits cell proliferation, blocks aberrant activation of JAK2 signaling pathway, and shows therapeutic potential in mouse models for MPNs treatment.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Cell Biology
Shaneice R. Mitchell, Jayakrishnan Gopakumar, Siddhartha Jaiswal
Summary: In the multi-hit model of carcinogenesis, identifying precancerous states such as Clonal Hematopoiesis of Indeterminate Potential (CHIP) is crucial for early detection of at-risk individuals. Research has shown that understanding the progression of CHIP to hematological malignancy can help identify high-risk individuals and lead to the development of preemptive targeted therapies.
CURRENT OPINION IN GENETICS & DEVELOPMENT
(2021)
Review
Oncology
Inderpreet Singh, Abhay Singh
Summary: This article summarizes the current knowledge about clonal hematopoiesis of indeterminate potential (CHIP), its association with cardiovascular disease (CVD), and other outcomes, pathogenesis, postulated mechanisms of various pathologies, current knowledge gaps, possible targets of intervention, and therapeutic implications. Recently, CHIP has been identified as an independent risk factor for CVD and is associated with various other pathologies. CHIP is a clonal expansion of blood cells with leukemogenic mutations but without evidence of malignancy, and it is known to increase the inflammatory state and risk of CVD.
CURRENT ONCOLOGY REPORTS
(2023)
Article
Cell Biology
Ana Guijarro-Hernandez, Laura Eder-Azanza, Cristina Hurtado, David Navarro-Herrera, Begona Ezcurra, Francisco Javier Novo, Juan Cabello, Jose Luis Vizmanos
Summary: There is increasing evidence that Ph-negative myeloproliferative neoplasms (MPNs) are characterized by disruption of multiple molecular mechanisms. In this study, patient-like calreticulin mutations were introduced into a C. elegans model lacking JAK2 and MPL orthologs. Transcriptomic analysis revealed genes and processes associated with MPN pathogenesis, some of which were validated through qPCR. This research provides a new experimental model for studying JAK2/MPL-independent mechanisms of mutant calreticulin.