Review
Hematology
Andrew J. Murphy, Dragana Dragoljevic, Pradeep Natarajan, Nan Wang
Summary: Hematopoiesis is the process of blood production, but the susceptibility of hematopoietic stem cells to mutations can lead to clonal hematopoietic disorders. Clonal hematopoiesis is associated with aging, where mutant stem cells produce a small portion of mature immune cells. People with clonal hematopoiesis have an increased risk of mortality due to cardiovascular disease.
THROMBOSIS AND HAEMOSTASIS
(2022)
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)
Review
Medical Laboratory Technology
Seyedmohammad Saadatagah, Christie M. Ballantyne
Summary: Age is a crucial risk factor for cardiovascular disease, as genetic mutations occur with aging, leading to somatic mosaicism. Clonal hematopoiesis resulting from somatic mutations, known as CHIP, has been associated with an increased risk of cardiovascular disease. Recent advances in exome-sequencing projects have enabled the study of CHIP frequency, gene-specific analyses, and potential therapeutic implications for preventing cardiovascular disease.
TRANSLATIONAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Xiongkai Yu, Ningjing Qian, Yaping Wang
Summary: Clonal hematopoiesis is a prevalent disease associated with all-cause death and has strong associations with cardiovascular disease. This review summarizes the latest research on clonal hematopoiesis, discusses its strong association with accelerated cardiovascular disease, and rationalizes the intervention of clonal hematopoiesis based on existing evidence, which may be beneficial for future treatment.
MOLECULAR BIOLOGY REPORTS
(2023)
Review
Oncology
Sarah C. Reed, Sarah Croessmann, Ben Ho Park
Summary: Clonal hematopoiesis of indeterminate potential (CHIP) is the expansion of leukemia-associated somatic mutations in healthy individuals, which can lead to increased risk of hematologic malignancy, cardiovascular disease, and mortality. Recent research has found high rates of CHIP in patients with solid tumors and suggests a potential role in inflammation and solid tumor biology.
CLINICAL CANCER RESEARCH
(2023)
Article
Cell Biology
Stefan Kuhnert, Siavash Mansouri, Michael A. Rieger, Rajkumar Savai, Edibe Avci, Gabriela Diaz-Pina, Manju Padmasekar, Mario Looso, Stefan Hadzic, Till Acker, Stephan Klatt, Jochen Wilhelm, Ingrid Fleming, Natascha Sommer, Norbert Weissmann, Claus Vogelmeier, Robert Bals, Andreas Zeiher, Stefanie Dimmeler, Werner Seeger, Soni S. Pullamsetti
Summary: This study found an increased incidence of CHIP mutations in COPD patients, which are associated with hypomethylation of PLD5, leading to elevated levels of glycerol phosphocholine, pro-inflammatory cytokines, and deteriorating lung function.
Review
Biology
Luka Komic, Marko Kumric, Hrvoje Urlic, Azer Rizikalo, Marko Grahovac, Jelena Kelam, Marion Tomicic, Doris Rusic, Tina Ticinovic Kurir, Josko Bozic
Summary: The clonal hematopoiesis of indeterminate potential (CHIP) refers to the presence of detectable somatic mutations in genes associated with hematologic cancers in individuals without any apparent evidence of such conditions. Studies have shown that the frequently altered genes in CHIP are also associated with an increased risk of cardiovascular diseases, type 2 diabetes mellitus, myeloid malignancies, and obesity. The shared pathogenetic mechanisms of obesity and CHIP contribute to the development of these conditions.
Article
Urology & Nephrology
Bryan Kestenbaum, Alexander G. Bick, Caitlyn Vlasschaert, Michael J. Rauh, Matthew B. Lanktree, Nora Franceschini, Moore B. Shoemaker, Raymond C. Harris Jr, Bruce M. Psaty, Anna Koettgen, Pradeep Natarajan, Cassianne Robinson-Cohen
Summary: This study found an association between clonal hematopoiesis and kidney function decline in the general population.
AMERICAN JOURNAL OF KIDNEY DISEASES
(2023)
Article
Hematology
Mridul Agrawal, Abhishek Niroula, Pierre Cunin, Marie McConkey, Veronica Shkolnik, Peter G. Kim, Waihay J. Wong, Lachelle D. Weeks, Amy E. Lin, Peter G. Miller, Christopher J. Gibson, Aswin Sekar, Inga-Marie Schaefer, Donna Neuberg, Richard M. Stone, Alexander G. Bick, Md Mesbah Uddin, Gabriel K. Griffin, Siddhartha Jaiswal, Pradeep Natarajan, Peter A. Nigrovic, Deepak A. Rao, Benjamin L. Ebert
Summary: Gout is a common inflammatory arthritis caused by hyperuricemia. This study found that CHIP, a condition related to hematologic cancers and cardiovascular disease, is associated with an increased risk of gout. Additionally, MSU crystals lead to elevated IL-1β levels in Tet2 knockout murine models.
Review
Biochemistry & Molecular Biology
Yi-Chun Huang, Chao-Yung Wang
Summary: Recent studies have highlighted the important roles of telomere, CHIP, and atherosclerosis in cardiovascular disease. Telomere attrition is associated with CHIP, commonly observed in elderly patients. Telomeres, CHIP, and atherosclerosis contribute to chronic inflammation and proinflammatory cytokine expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Hematology
Thomas L. Olson, HeeJin Cheon, Jeffrey C. Xing, Kristine C. Olson, Umadevi Paila, Cait E. Hamele, Yaseswini Neelamraju, Bryna C. Shemo, Matt Schmachtenberg, Shriram K. Sundararaman, Mariella F. Toro, Cheryl A. Keller, Emily A. Farber, Suna Onengut-Gumuscu, Francine E. Garrett-Bakelman, Ross C. Hardison, David J. Feith, Aakrosh Ratan, Thomas P. Loughran
Summary: Chronic natural killer large granular lymphocyte (NK-LGL) leukemia is a rare disorder characterized by prolonged expansion of clonal NK cells, with unique mutations such as TET2 and STAT3 playing important roles in its pathogenesis.
Review
Medical Laboratory Technology
Yasminka A. Jakubek, Alexander P. Reiner, Michael C. Honigberg
Summary: Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are somatic mutations associated with aging, which increase the risk of chronic aging-related conditions and mortality. Age, genetic factors, and environmental factors such as smoking and diet play roles in the occurrence and progression of these mutations. Recent studies have identified genetic variants related to CHIP and mCAs, which involve genes regulating cell cycle and proliferation, hematopoietic progenitor cell regulation, DNA damage repair, and telomere maintenance. Understanding the genetic and environmental correlates of CHIP/mCAs may help reduce the risk and burden of chronic diseases associated with these somatic phenomena.
TRANSLATIONAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Francesco Vieceli Dalla Sega, Domenico Palumbo, Francesca Fortini, Ylenia D'Agostino, Paolo Cimaglia, Luisa Marracino, Paolo Severi, Oriana Strianese, Roberta Tarallo, Giovanni Nassa, Giorgio Giurato, Giovanni Pecoraro, Serena Caglioni, Elisa Mikus, Alberto Albertini, Gianluca Campo, Roberto Ferrari, Paola Rizzo, Alessandro Weisz, Francesca Rizzo
Summary: Clonal hematopoiesis of indeterminate potential (CHIP) is associated with atherosclerosis and coronary calcification, and is commonly found in patients with calcific aortic valve disease (CAVD) who have a poor prognosis after valve replacement. In addition, CHIP often leads to a broad immune response in the aortic valve, suggesting a possible role of B cells in CHIP-induced inflammation.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Claire L. Leiser, Eric A. Whitsel, Alexander Reiner, Stephen S. Rich, Jerome I. Rotter, Kent D. Taylor, Russel P. Tracy, Charles Kooperberg, Albert Vernon Smith, JoAnn E. Manson, Josyf C. Mychaleckyj, Alexander G. Bick, Adam A. Szpiro, Joel D. Kaufman
Summary: This study aimed to estimate the association between air pollution and clonal hematopoiesis of indeterminate potential (CHIP). The results showed no evidence of an association between air pollution and CHIP prevalence in two large observational cohorts.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2023)
Article
Clinical Neurology
Ernst Mayerhofer, Christoph Strecker, Heiko Becker, Marios K. Georgakis, Md Mesbah Uddin, Michael M. Hoffmann, Niroshan Nadarajah, Manja Meggendorfer, Torsten Haferlach, Jonathan Rosand, Pradeep Natarajan, Christopher D. Anderson, Andreas Harloff, Gregor Hoermann
Summary: Genetic screening in young stroke patients revealed a 3-fold higher prevalence of clonal hematopoiesis compared to the general population. About 4.4% of patients had high-risk clonal hematopoiesis and 1% had covert myeloproliferative neoplasms, requiring specific treatment. These findings highlight the diagnostic and therapeutic value of genetic screening in young stroke patients.
Article
Allergy
Sarah K. Baxter, Tom Walsh, Silvia Casadei, Mary M. Eckert, Eric J. Allenspach, David Hagin, Gesmar Segundo, Ming K. Lee, Suleyman Gulsuner, Brian H. Shirts, Kathleen E. Sullivan, Michael D. Keller, Troy R. Torgerson, Mary-Claire King
Summary: This study identified damaging germline mutations in 27 genes in about 39% of patients with childhood-onset immune dysregulation, polyendocrinopathy, and enteropathy. Many of these genes had not been previously associated with the disease. Genetic diagnoses of these patients have clinical implications and can potentially alter therapeutic management, providing targeted treatments and recommendations for hematopoietic cell transplantation.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Genetics & Heredity
Michal Yechieli, Suleyman Gulsuner, Hilla Ben-Pazi, Aviva Fattal, Adi Aran, Alla Kuzminsky, Liora Sagi, Dafna Guttman, Nira Schneebaum Sender, Varda Gross-Tsur, Tehila Klopstock, Tom Walsh, Paul Renbaum, Sharon Zeligson, Lilach Shemer Meiri, Dorit Lev, Dorit Shmueli, Luba Blumkin, Amnon Lahad, Mary-Claire King, Ephrat Lahad Levy, Reeval Segel
Summary: Patients with cryptogenic cerebral palsy had a 58% yield of clinically significant genetic findings through chromosomal microarray and trio whole exome sequencing, with a majority of the mutations being de novo. Those with comorbidities had a higher yield compared to those with pure motor CP. Genetic diagnoses were more common in patients with congenital anomalies or major dysmorphic features, with trio WES showing a higher yield than CMA in overall cases.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Hematology
Alexander E. Perl, Richard A. Larson, Nikolai A. Podoltsev, Stephen Strickland, Eunice S. Wang, Ehab Atallah, Gary J. Schiller, Giovanni Martinelli, Andreas Neubauer, Jorge Sierra, Pau Montesinos, Christian Recher, Sung-Soo Yoon, Naoko Hosono, Masahiro Onozawa, Shigeru Chiba, Hee-Je Kim, Nahla Hasabou, Qiaoyang Lu, Ramon Tiu, Mark J. Levis
Summary: The follow-up of the ADMIRAL trial after 2 years demonstrates that gilteritinib is a safe and effective treatment option for patients with relapsed/refractory FLT3-mutation-positive AML. Gilteritinib therapy provides superior overall survival and long-term remission compared to salvage chemotherapy, especially when used as post-HSCT maintenance.
Letter
Hematology
Carlo Gambacorti-Passerini, Franck Emmanuel Nicolini, Richard A. Larson, Andrea Aroldi, Diletta Fontana, Rocco Piazza, Philipp le Coutre, Laura Antolini, Sarit Assouline
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Oncology
Gabriela E. S. Felix, Rodrigo Santa Cruz Guindalini, Yonglan Zheng, Tom Walsh, Elisabeth Sveen, Taisa Manuela Machado Lopes, Juliana Cortes, Jing Zhang, Polyanna Carozo, Irlania Santos, Thais Ferreira Bonfim, Bernardo Garicochea, Maria Betania Pereira Toralles, Roberto Meyer, Eduardo Martins Netto, Kiyoko Abe-Sandes, Mary-Claire King, Ivana Lucia de Oliveira Nascimento, Olufunmilayo Olopade
Summary: The study reveals the prevalence and heterogeneous spectrum of pathogenic variants among self-reported African-descended women in Northeast Brazil, with high-risk genes including BRCA1, BRCA2, PALB2, and TP53.
BREAST CANCER RESEARCH AND TREATMENT
(2022)
Article
Hematology
Zachary D. Epstein-Peterson, Andriy Derkach, Susan Geyer, Krzysztof Mrozek, Jessica Kohlschmidt, Jae H. Park, Sridevi Rajeeve, Eytan M. Stein, Yanming Zhang, Harry Iland, Lynda J. Campbell, Richard A. Larson, Xavier Poire, Bayard L. Powell, Wendy Stock, Richard M. Stone, Martin S. Tallman
Summary: In this study, a pooled analysis of ATO-treated APL patients revealed that patients with a complex karyotype had inferior event-free survival, while the presence of additional cytogenetic abnormalities did not significantly impact survival. These findings emphasize the importance of conducting full karyotypic analysis in all APL patients and highlight the need for novel treatment strategies to overcome the adverse effects of APL with a complex karyotype.
Article
Hematology
Ellen K. Ritchie, Heidi D. Klepin, Elizabeth Storrick, Brittny Major, Jennifer Le-Rademacher, Martha Wadleigh, Alison Walker, Richard A. Larson, Gail J. Roboz
Summary: Geriatric assessment (GA) can predict survival among older adults with acute myeloid leukemia (AML) treated intensively. This study evaluated the predictive utility of GA among older adults treated with low-intensity therapy, finding that comorbidity, cognition, and self-reported function were associated with survival and can be used as screening measures for older adults receiving lower-intensity AML therapies.
Article
Hematology
Stephane de Botton, Pau Montesinos, Andre C. Schuh, Cristina Papayannidis, Paresh Vyas, Andrew H. Wei, Hans Ommen, Sergey Semochkin, Hee-Je Kim, Richard A. Larson, Jaime Koprivnikar, Olga Frankfurt, Felicitas Thol, Joerg Chromik, Jenny Byrne, Arnaud Pigneux, Xavier Thomas, Olga Salamero, Maria Belen Vidriales, Vadim Doronin, Hartmut Doehner, Amir T. Fathi, Eric Laille, Xin Yu, Maroof Hasan, Patricia Martin-Regueira, Courtney D. DiNardo
Summary: This study compared the efficacy of the oral IDH2 inhibitor enasidenib with conventional care regimens (CCR) in older patients with late-stage mutant-IDH2 AML. Enasidenib significantly improved event-free survival, time to treatment failure, overall response rate, hematologic improvement, and transfusion independence compared to CCR. However, there was no significant difference in overall survival, possibly due to early dropout and subsequent AML-directed therapies.
Article
Hematology
Misha C. Tran, Yasmin Hasan, Amy Wang, Kamil Yenice, Julien Partouche, Wendy Stock, Richard A. Larson, Satyajit Kosuri, James L. LaBelle, Justin Kline, Peter A. Riedell, Andrew S. Artz, Ralph Weichselbaum, Michael R. Bishop, Bulent Aydogan, Hongtao Liu
Summary: Relapse after allo-SCT is a common issue, and a second SCT can be considered for treatment. The study explored the feasibility of combining IM-TMI with fludarabine and melphalan for conditioning in patients undergoing a second or greater allo-SCT. The results showed that the combination therapy was feasible and achieved favorable outcomes.
Article
Immunology
Tal Freund, Sarah K. Baxter, Tom Walsh, Hana Golan, Joseph Kapelushnik, Michal Abramsohn-Goldenberg, Shira Benor, Nadav Sarid, Ron Ram, Yifat Alcalay, Reeval Segel, Paul Renbaum, Polina Stepensky, Mary-Claire King, Troy R. Torgerson, David Hagin
Summary: Pathogenic variants in the LRBA gene can lead to diverse clinical symptoms with variable disease severity. A founder allele of the LRBA gene was found in the Georgian Jewish population and may be associated with increased susceptibility to malignancies.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Hematology
Andrew J. Shih, Tomi Jun, Andrew D. Skol, Riyue Bao, Lei Huang, Sapana Vora, Megan E. McNerney, Eric A. Hungate, Michelle M. Le Beau, Richard A. Larson, Aaron Elliott, Hsiao-Mei Lu, Robert Huether, Felicia Hernandez, Friedrich Stolzel, James M. Allan, Kenan Onel
Summary: Some patients with therapy-related myeloid neoplasms (t-MN) may have unsuspected inherited cancer predisposition syndrome (CPS). A set of clinical criteria has been proposed to identify t-MN patients with high risk of CPS (HR-CPS). Among the identified HR-CPS patients, 37% had pathogenic or likely pathogenic variants, compared to 0% in the low-risk CPS patients. These simple clinical criteria help identify t-MN patients most likely to benefit from genetic testing for inherited CPS.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Jorge E. Cortes, Andreas Hochhaus, Naoto Takahashi, Richard A. Larson, Ghayas C. Issa, Felice Bombaci, Nicholas Ramscar, Sophie Ifrah, Timothy P. Hughes
Summary: Asciminib, a BCR-ABL1 inhibitor that works through the STAMP mechanism, has shown favorable efficacy and safety in patients with chronic myeloid leukemia in chronic phase. The ongoing ASC4FIRST trial aims to compare the effectiveness of Asciminib with investigator-selected TKIs in newly diagnosed patients with chronic myeloid leukemia.
Article
Otorhinolaryngology
Ryan J. Carlson, Tom Walsh, Jessica B. Mandell, Amal Aburayyan, Ming K. Lee, Suleyman Gulsuner, David L. Horn, Henry C. Ou, Kathleen C. Y. Sie, Lisa Mancl, Jay Rubinstein, Mary-Claire King
Summary: Most childhood-onset bilateral sensorineural hearing loss in the US is genetic. The study aimed to identify the genetic causes of hearing loss, assess its severity and progression, and evaluate cochlear implant success based on genotype. The results suggest that genetic diagnosis can now be integrated into precision medical care for childhood-onset hearing loss.
JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY
(2023)
Article
Oncology
Naval G. Daver, Paresh Vyas, Suman Kambhampati, Monzr M. Al Malki, Richard A. Larson, Adam S. Asch, Gabriel Mannis, Wanxing Chai-Ho, Tiffany N. Tanaka, Terrence J. Bradley, Deepa Jeyakumar, Eunice S. Wang, Kendra Sweet, Hagop M. Kantarjian, Guillermo Garcia-Manero, Rami Komrokji, Guan Xing, Giridharan Ramsingh, Camille Renard, Joshua F. Zeidner, David A. Sallman
Summary: Magrolimab combined with azacitidine showed promising efficacy and tolerability in patients with untreated AML ineligible for intensive chemotherapy, including those with TP53 mutations.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Hematology
Alexander E. Perl, Richard A. Larson, Nikolai A. Podoltsev, Stephen Strickland, Eunice S. Wang, Ehab Atallah, GaryJ. Schiller, Giovanni Martinelli, Andreas Neubauer, Jorge Sierra, Pau Montesinos, Christian Recher, Sung-Soo Yoon, Yoshinobu Maeda, Naoko Hosono, Masahiro Onozawa, Takayasu Kato, Hee-Je Kim, Nahla Hasabou, Rishita Nuthethi, Ramon Tiu, Mark J. Levis
Summary: The ADMIRAL trial investigated the efficacy of using the FLT3 inhibitor gilteritinib as maintenance therapy after hematopoietic stem cell transplantation (HSCT) in patients with relapsed or refractory FLT3-mutated AML. The results showed that gilteritinib maintenance therapy improved survival rates and was well-tolerated in patients post-HSCT.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
