Article
Biochemistry & Molecular Biology
Elena V. Koroleva, Yuri V. Kornoushenko, Anna D. Karpenko, Ivan P. Bosko, Julia V. Siniutsich, Zhanna V. Ignatovich, Alexander M. Andrianov
Summary: An integrated computational approach was used to identify potential inhibitors of Bcr-Abl tyrosine kinase, an enzyme involved in chronic myeloid leukemia. Five compounds were found to effectively block the enzyme activity and exhibit high binding affinity comparable to FDA-approved kinase inhibitors. These compounds may serve as good scaffolds for the design of novel anticancer agents.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Oncology
Christian Boni, Massimiliano Bonifacio, Marzia Vezzalini, Luigi Scaffidi, Luisa Tomasello, Laurie L. Parker, Diego Boscarino, Dino Paladin, Mauro Krampera, Claudio Sorio
Summary: Chronic myeloid leukemia (CML) is caused by the fusion tyrosine kinase BCR::ABL1 produced by t(9;22). However, the direct measurement of BCR::ABL1 kinase activity in chronic phase (CP) CML has never been achieved due to degradation in mature leukocytes. In this study, a method was developed to preserve BCR::ABL1 protein in primary CP-CML samples, allowing for the detection of specific kinase activity using a selective substrate. The results showed that BCR::ABL1 kinase activity was barely detectable in CP-CML compared to Ph+ acute lymphoblastic leukemia samples.
FRONTIERS IN ONCOLOGY
(2022)
Article
Medicine, General & Internal
Jeannig Berrou, Melanie Dupont, Hanane Djamai, Emilie Adiceam, Veronique Parietti, Anna Kaci, Emmanuelle Clappier, Jean-Michel Cayuela, Andre Baruchel, Fabrice Paublant, Renaud Prudent, Jacques Ghysdael, Claude Gardin, Herve Dombret, Thorsten Braun
Summary: This study demonstrates that LIMKi CEL_Amide has anti-leukemic effects in Ph+ ALL models when combined with BCR::ABL-targeting TKIs, showing promising synergy that warrants further investigation.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Pelin Ayaz, Agatha Lyczek, YiTing Paung, Victoria R. Mingione, Roxana E. Iacob, Parker W. de Waal, John R. Engen, Markus A. Seeliger, Yibing Shan, David E. Shaw
Summary: The authors used molecular dynamics simulations to study the binding process of Abl kinase with the cancer drug imatinib. The simulations revealed that imatinib induces a large conformational change of the protein and identified a region in Abl kinase that is structurally unstable during binding. Mutations in this region confer imatinib resistance by exacerbating structural instability.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Yosuke Tanaka, Reina Takeda, Tsuyoshi Fukushima, Keiko Mikami, Shun Tsuchiya, Moe Tamura, Keito Adachi, Terumasa Umemoto, Shuhei Asada, Naoki Watanabe, Soji Morishita, Misa Imai, Masayoshi Nagata, Marito Araki, Hitoshi Takizawa, Tomofusa Fukuyama, Chrystelle Lamagna, Esteban S. Masuda, Ryoji Ito, Susumu Goyama, Norio Komatsu, Tomoiku Takaku, Toshio Kitamura
Summary: Leukemia stem cells in chronic myeloid leukemia are resistant to imatinib, but can be eliminated by combining imatinib with IRAK1/4 inhibitors that inhibit the IRAK1/4-NF-kappa B-PD-L1 signaling pathway.
NATURE COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Francois Pierre Combes, Ying Fei Li, Matthias Hoch, Sebastien Lorenzo, Yu-Yun Ho, Sherwin K. B. Sy
Summary: Asciminib has potent activity against the T315I mutation in chronic myeloid leukemia patients. A longitudinal pharmacokinetic/pharmacodynamic model was developed to characterize the exposure-efficacy relationship of Asciminib. The model demonstrated the appropriateness of different doses for patients with or without the T315I mutation.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Biochemistry & Molecular Biology
Xiao-Liang Xu, Yu-Jing Cao, Wen Zhang, Guo-Wu Rao
Summary: Tyrosine kinases expressed by BCR-ABL fusion genes play a crucial role in chronic myelogenous leukemia (CML), and inhibiting their activity has become an effective treatment method. Various inhibitors have been developed to overcome drug resistance, with newer options like flumatinib and radotinib entering clinical trials.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Nafia Gokce Ulusoy, Safiye Emirdag, Ece Sozer, Mohamed O. Radwan, Halilibrahim Ciftci, Mehran Aksel, Ali Ozmen, Nurettin Yayli, Tamer Karayildirim, Ozgen Alankus, Hiroshi Tateishi, Masami Otsuka, Mikako Fujita, Belgin Sever, Serap Sahin Bolukbasi
Summary: In this study, new gypsogenin derivatives were synthesized and their anticancer effects against CML cells were evaluated. Compound 6l was found to be the most effective anti-leukemic agent against CML cells, with less cytotoxicity towards healthy cells compared to imatinib. Furthermore, compound 6l significantly enhanced apoptosis in CML cells and inhibited Abl TK activity.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Cardiac & Cardiovascular Systems
Wenying Jin, Sen Yang, Chao Yu, Tiangang Zhu, Qian Jiang
Summary: This study found that the use of dasatinib therapy is associated with pulmonary hypertension (PH) in patients with chronic myeloid leukemia (CML). Increasing age, pericardial effusion, cardiopulmonary comorbidities, and dasatinib as >= 3rd-line therapy were identified as risk factors for PH in these patients.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Oncology
Stephanie M. Smith, Nobuko Hijiya, Kathleen M. Sakamoto
Summary: Targeted therapy has greatly improved outcomes for pediatric CML, but has also raised several clinical questions, including the possibility of treatment-free remission and long-term health implications of prolonged TKI exposure at a young age.
CURRENT ONCOLOGY REPORTS
(2021)
Article
Oncology
Ryan Yen, Sarah Grasedieck, Andrew Wu, Hanyang Lin, Jiechuang Su, Katharina Rothe, Helen Nakamoto, Donna L. Forrest, Connie J. Eaves, Xiaoyan Jiang
Summary: This study analyzed differentially expressed miRNAs in CML patients, showing that the combination of miR-145 and miR-708 effectively predicts response to NL in treatment-naive patients, while miR-150 and miR-185 are significant classifiers at 1 month and 3 months post-NL therapy.
Review
Pediatrics
Shuvadeep Ganguly, Archana Sasi, Deepam Pushpam, Sameer Bakhshi
Summary: This article describes the diagnosis and treatment methods of Philadelphia chromosome positive acute lymphoblastic lymphoma (Ph+ ALL) in children, including conventional karyotyping and BCR-ABL1 translocation detection, as well as using chemotherapy and hematopoietic stem cell transplantation to control and treat the disease.
INDIAN JOURNAL OF PEDIATRICS
(2023)
Article
Biotechnology & Applied Microbiology
Zhe Wang, Ting Liu, Wenbing Liu, Xin Gao, Li Wan, Shaowei Qiu, Yang Song, Runxia Gu, Zheng Tian, Min Wang, Jianxiang Wang, Yingchang Mi, Shuning Wei
Summary: We reported a case of AML with NPM1 mutation and a subclonal gene rearrangement involving the PDGFRB gene. We identified a novel fusion gene, STRN3::PDGFRB, resulting from a chromosomal rearrangement. The new fusion protein exhibited distinct localization and had leukemogenic effects. The combination of Imatinib and Selinexor showed a marked synergistic effect in vitro.
CANCER GENE THERAPY
(2023)
Article
Hematology
Simona Soverini, Margherita Martelli, Luana Bavaro, Caterina De Benedittis, Cristina Papayannidis, Chiara Sartor, Federica Sora, Francesco Albano, Sara Galimberti, Elisabetta Abruzzese, Mario Annunziata, Sabina Russo, Manuela Stulle, Annalisa Imovilli, Massimiliano Bonifacio, Elena Maino, Fabio Stagno, Claudia Maria Basilico, Erika Borlenghi, Claudio Fozza, Flavio Mignone, Roberta Minari, Stefania Stella, Michele Baccarani, Michele Cavo, Giovanni Martinelli
Summary: Our study compared the results of Sanger sequencing and next-generation sequencing in Ph+ ALL patients, revealing that NGS provides more accurate and sensitive detection of mutations, particularly in cases of hematologic resistance and minimal residual disease.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Oncology
Angela McLigeyo, Jamilla Rajab, Peter Oyiro, Mohammed Ezzi, Yatich Bett, Matilda Ong'ondi, Andrew Odhiambo, Sitna Mwanzi, Nicholas Othieno-Abinya
Summary: This study analyzed the baseline characteristics and factors associated with cytopenia in Chronic Myeloid Leukemia patients treated with imatinib. The results showed no significant differences in gender, age, marital status, occupation, and education level between patients with and without cytopenia. Multivariable analysis revealed that baseline anemia, neutropenia, thrombocytopenia, and thrombocytosis increased the odds of developing cytopenia.
Article
Cardiac & Cardiovascular Systems
J. Antonio Gutierrez, Marc D. Samsky, Ryan D. Schulteis, Lin Gu, Rajesh V. Swaminathan, Aaron W. Aday, Sunil V. Rao
Summary: This study aimed to characterize the incidence, timecourse, and outcomes of VTE during the COVID-19 pandemic in a national healthcare system using data from the Veterans Affairs Administration.
AMERICAN HEART JOURNAL
(2021)
Article
Hematology
Aaron W. Aday, Edward K. Duran, Martin Van Denburgh, Eunjung Kim, William G. Christen, JoAnn E. Manson, Paul M. Ridker, Aruna D. Pradhan
Summary: The study found that elevated plasma homocysteine levels are associated with VTE events in middle-aged and older women, particularly in unprovoked cases.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Michael G. Levin, Verena Zuber, Venexia M. Walker, Derek Klarin, Julie Lynch, Rainer Malik, Aaron W. Aday, Leonardo Bottolo, Aruna D. Pradhan, Martin Dichgans, Kyong-Mi Chang, Daniel J. Rader, Philip S. Tsao, Benjamin F. Voight, Dipender Gill, Stephen Burgess, Scott M. Damrauer
Summary: The study identified ApoB as the major lipoprotein fraction causally responsible for both PAD and CAD risk. Different associations were found between ApoB-lowering drug targets and ApoB-containing lipoprotein subfractions with atherosclerotic cardiovascular disease, suggesting possible differences in the role of lipoproteins in the pathogenesis of PAD and CAD.
Article
Cardiac & Cardiovascular Systems
Aaron W. Aday, Kunihiro Matsushita
Summary: PAD is increasingly recognized as a major cause of cardiovascular morbidity and mortality worldwide. The focus on PAD in recent years has led to new epidemiological insights and highlighted the importance of polyvascular disease in cardiovascular research and clinical practice. PAD may present similar or even greater risk compared to coronary artery disease or stroke.
CIRCULATION RESEARCH
(2021)
Article
Medicine, General & Internal
Patrick R. Lawler, Ewan C. Golighe, Jeffrey S. Berge, Matthew D. Neal, Bryan J. McVerry, Jose C. Nicolau, Michelle N. Gong, Marc Carrier, Robert S. Rosenson, Harmony R. Reynolds, Alexis F. Turgeon, Jorge Escobedo, David T. Huang, Charlotte A. Bradbury, Brett L. Houston, Lucy Z. Kornblith, Anand Kumar, Susan R. n Kah, Mary Cushman, Zoe McQuilten, Arthur S. Slutsky, Keri S. Kim, Anthony C. Gordon, Bridget-Anne Kirwan, Maria M. Brooks, Alisa M. Higgins, Roger J. Lewis, Elizabeth Lorenzi, Scott M. Berry, Lindsay R. Berry, Derek C. Angus, Colin J. McArthur, Steven A. Webb, Michael E. Farkouh, Judith S. Hochman, Ryan Zarychanski, Aaron W. Aday, Farah Al-Beidh, Djillali Annane, Yaseen M. Arabi, Diptesh Aryal, Lisa Baumann Kreuziger, Abi Beane, Zahra Bhimani, Shailesh Bihari, Henny H. Billett, Lindsay Bond, Marc Bonten, Frank Brunkhorst, Meredith Buxton, Adrian Buzgau, Lana A. Castellucci, Sweta Chekuri, Jen-Ting Chen, Allen C. Cheng, Tamta Chkhikvadzw, Benjamin Coiffard, Todd W. Costantini, Sophie de Brouwer, Lennie P. G. Derde, Michelle A. Detry, Abhijit Duggal, Vladimir Dzavik, Mark B. Effron, Lise J. Estcourt, Brendan M. Everett, Dean A. Fergusson, Mark Fitzgerald, Robert A. Fowler, Jean P. Galanaud, Benjamin T. Galen, Sheetal Gandotra, Sebastian Garcia-Madrona, Timothy D. Girard, Lucas C. Godoy, Andrew L. Goodman, Herman Goossens, Cameron Green, Yonatan Y. Greenstein, Peter L. Gross, Naomi M. Hamburg, Rashan Haniffa, George Hanna, Nicholas Hanna, Sheila M. Hegde, Carolyn M. Hendrickson, R. Duncan Hite, Alexander A. Hindenburg, Aluko A. Hope, James M. Horowitz, Christopher M. Horvat, Kristin Hudock, Beverley J. Hunt, Mansoor Husain, Robert C. Hyzy, Vivek N. Iyer, Jeffrey R. Jacobson, Devachandran Jayakumar, Norma M. Keller, Akram Khan, Yuri Kim, Andrei L. Kindzelski, Andrew J. Kin, M. Margaret Knudson, Aaron E. Kornblith, Vidya Krishnan, Matthew E. Kutcher, Michael A. Laffan, Francois Lamontagne, Gregoire Le Gal, Christine M. Leeper, Eric S. Leifer, George Lim, Felipe Gallego Lima, Kelsey Linstrum, Edward Litton, Jose Lopez-Sendon, Jose L. Lopez-Sendon Moreno, Sylvain A. Lother, Saurabh Malhotra, Miguel Marcos, Andrea Saud Marinez, John C. Marshall, Nicole Marten, Michael A. Matthay, Daniel F. McAuley, Emily G. McDonald, Anna McGlothlin, Shay P. McGuinness, Saskia Middeldorp, Stephanie K. Montgomery, Steven C. Moore, Raquel Morillo Guerreor, Paul R. Mouncey, Srinivas Murthy, Girish B. Nair, Rahul Nair, Alistair D. Nichol, Brenda Nunez-Garcia, Ambarish Pandey, Pauline K. Park, Rachael L. Parke, Jane C. Parker, Sam Parnia, Jonathan D. Paul, Yessica S. Perez Gonzalez, Mauricio Pompilio, Matthew E. Prekker, John G. Quigley, Natalia S. Rost, Kathryn Rowan, Fernanda O. Santos, Marlene Santos, Mayler Olombrada Santos, Lewis Satterwhite, Christina T. Saunders, Roger E. G. Schutgens, Christopher W. Seymour, Deborah M. Siegal, Delcio G. Silva, Manu Shankar-Hari, John P. Sheehan, Aneesh B. Singhal, Dayna Solvaso, Simon J. Stanworth, Tobias Tritschler, Anne M. Turner, Wilma Van Bentum-Puijk, Frank L. van de Veerdonk, Sean van Diepen, Gloria Vazquez-Grande, Lana Wahid, Vanessa Wareham, Bryan J. Wells, R. Jay Widmer, Jennifer G. Wilson, Eugene Yuriditsky, Fernando G. Zampieri
Summary: This study showed that therapeutic-dose anticoagulation with heparin in non-critically ill patients with Covid-19 increased the likelihood of survival to hospital discharge and reduced the need for cardiovascular or respiratory organ support compared to usual-care thromboprophylaxis.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Quinn S. Wells, Minoo Bagheri, Aaron W. Aday, Deepak K. Gupta, Christian M. Shaffer, Wei-Qi Wei, Nataraja Sarna Vaitinadin, Sadiya S. Khan, Philip Greenland, Thomas J. Wang, C. Michael Stein, Dan M. Roden, Jonathan D. Mosley
Summary: The study found that the polygenic risk scores can improve model discrimination for coronary atherosclerosis among young adults, but the improvements are smaller than those associated with modifiable risk factors.
CIRCULATION-GENOMIC AND PRECISION MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Connie W. Tsao, Aaron W. Aday, Zaid I. Almarzooq, Alvaro Alonso, Andrea Z. Beaton, Marcio S. Bittencourt, Amelia K. Boehme, Alfred E. Buxton, April P. Carson, Yvonne Commodore-Mensah, Mitchell S. V. Elkind, Kelly R. Evenson, Chete Eze-Nliam, Jane F. Ferguson, Giuliano Generoso, Jennifer E. Ho, Rizwan Kalani, Sadiya S. Khan, Brett M. Kissela, Kristen L. Knutson, Deborah A. Levine, Tene T. Lewis, Junxiu Liu, Matthew Shane Loop, Jun Ma, Michael E. Mussolino, Sankar D. Navaneethan, Amanda Marma Perak, Remy Poudel, Mary Rezk-Hanna, Gregory A. Roth, Emily B. Schroeder, Svati H. Shah, Evan L. Thacker, Lisa B. VanWagner, Salim S. Virani, Jenifer H. Voecks, Nae-Yuh Wang, Kristine Yaffe, Seth S. Martin
Summary: This article introduces the latest statistics on heart disease, stroke, and cardiovascular risk factors published by the American Heart Association in conjunction with the National Institutes of Health. The Statistical Update includes data on a range of clinical heart and circulatory disease conditions and their associated outcomes. It serves as a critical resource for the general public, policymakers, healthcare professionals, researchers, and others seeking the best available data.
Article
Cardiac & Cardiovascular Systems
J. Antonio Gutierrez, Ruff T. Christian, Aaron W. Aday, Lin Gu, Ryan D. Schulteis, Lu Shihai, Michaela Petrini, Albert Y. Sun, Rajesh Swaminathan, Daniel R. Katzenberger, Subhash Banerjee, Sunil Rao
Summary: This study aimed to evaluate the effect of an electronic support system on the prescription rates and adherence to oral anticoagulation therapy among patients with AF and atrial flutter. The results showed that the use of an electronic alert and shared decision-making tool significantly increased the prescription rate of anticoagulation therapy and supported high rates of adherence.
AMERICAN HEART JOURNAL
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Tara M. Mastracci, Sonia S. Anand, Aaron W. Aday
CANADIAN JOURNAL OF CARDIOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Amanda Morrison, Aaron W. Aday
Summary: Atherosclerotic peripheral artery disease (PAD) has different prevalence and clinical presentations between men and women. Women with PAD are more likely to experience functional limitations and clinical deterioration, and they receive less medical therapy. Inflammation and lipid profiles are associated with the development of PAD, and there are sex differences in these factors.
CANADIAN JOURNAL OF CARDIOLOGY
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Rachelle Crescenzi, Paula M. C. Donahue, Maria Garza, Niral J. Patel, Chelsea Lee, Kelsey Guerreso, Greg Hall, Yu Luo, Sheau-Chiann Chen, Karen L. Herbst, Michael Pridmore, Aaron W. Aday, Joshua A. Beckman, Manus J. Donahue
Summary: 3T MR lymphangiography can distinguish lipedema from obesity or lymphedema. This study used MRI technology to identify characteristic features in patients with lipedema.
JOURNAL OF MAGNETIC RESONANCE IMAGING
(2023)
Article
Medicine, General & Internal
Aaron W. Aday, Meredith S. Duncan, Olga Patterson, Scott L. DuVall, Patrick R. Alba, Charles W. Alcorn, Hilary A. Tindle, Mark A. Creager, Marc P. Bonaca, Scott M. Damrauer, Quinn S. Wells, Adam Behroozian, Joshua A. Beckman, Matthew S. Freiberg
Summary: The risk of incident PAD varies by sex and race, with women having a lower risk compared to men and Black participants having a slightly higher risk compared to White participants, particularly for nontraumatic amputation. Diabetes and smoking are associated with incident PAD.
Article
Cardiac & Cardiovascular Systems
Connie W. Tsao, Aaron W. Aday, Zaid I. Almarzooq, Cheryl A. M. Anderson, Pankaj Arora, Christy L. Avery, Carissa M. Baker-Smith, Andrea Z. Beaton, Amelia K. Boehme, Alfred E. Buxton, Yvonne Commodore-Mensah, Mitchell S. V. Elkind, Kelly R. Evenson, Chete Eze-Nliam, Setri Fugar, Giuliano Generoso, Debra G. Heard, Swapnil Hiremath, Jennifer E. Ho, Rizwan Kalani, Dhruv S. Kazi, Darae Ko, Deborah A. Levine, Junxiu Liu, Jun Ma, Jared W. Magnani, Erin D. Michos, Michael E. Mussolino, Sankar D. Navaneethan, Nisha I. Parikh, Remy Poudel, Mary Rezk-Hanna, Gregory A. Roth, Nilay S. Shah, Marie-Pierre St-Onge, Evan L. Thacker, Salim S. Virani, Jenifer H. Voeks, Nae-Yuh Wang, Nathan D. Wong, Sally S. Wong, Kristine Yaffe, Seth S. Martin
Summary: The American Heart Association, in collaboration with the National Institutes of Health, releases annual statistics on heart disease, stroke, and cardiovascular risk factors. The Statistical Update provides the latest data on various heart and circulatory diseases and their outcomes, as well as information on core health behaviors and factors contributing to cardiovascular health.
Letter
Radiology, Nuclear Medicine & Medical Imaging
Rachelle Crescenzi, Paula C. Donahue, Aaron W. Aday, Yu Luo, Manus J. Donahue
JOURNAL OF MAGNETIC RESONANCE IMAGING
(2023)
Editorial Material
Peripheral Vascular Disease
Tara A. Holder, Aaron W. Aday, LeAnn S. Stokes