Article
Biochemistry & Molecular Biology
Georg J. Rottenaicher, Benedikt Weber, Florian Ruehrnoessl, Pamine Kazman, Ramona M. Absmeier, Manuel Hitzenberger, Martin Zacharias, Johannes Buchner
Summary: Specific mutations in the patient V-L domain can lead to protein destabilization and amyloid fibril formation, with the key disease-causing mutations located in the variable CDRs but impacting the dynamics of conserved core regions. These mutations do not necessarily propagate fibril formation by providing specific side chain interactions within the fibril structure, but rather destabilize the V-L domain in a way that increases the dynamics of framework regions, affecting the conformational changes needed for fibril core formation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Rosaria Russo, Margherita Romeo, Tim Schulte, Martina Maritan, Luca Oberti, Maria Monica Barzago, Alberto Barbiroli, Carlo Pappone, Luigi Anastasia, Giovanni Palladini, Luisa Diomede, Stefano Ricagno
Summary: This study demonstrates the specific binding of Cu2+ to the variable domain of amyloidogenic H7 with a sub-micromolar affinity using microscale thermophoresis, isothermal calorimetry and thermal melting. The binding of copper ions is just one of the several biochemical traits contributing to light chain amyloidosis soluble toxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Nicholas L. Yan, Reji Nair, Alan Chu, Ian A. Wilson, Kristen A. Johnson, Gareth J. Morgan, Jeffery W. Kelly
Summary: This study investigates the potential of finding small molecule kinetic stabilizers in immunoglobulin light chain amyloidosis, identifying coumarin-based compounds with potential therapeutic effects. Structural-activity relationship data reveals that these compounds bind at different sites in the LC dimer, exerting unique stabilizing effects on LCs.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Akifumi Kato, Kazumasa Ohtake, Yoshitaka Tanaka, Shigeyuki Yokoyama, Kensaku Sakamoto, Yasuhisa Shiraishi
Summary: This study successfully incorporated a novel amino acid into antibodies using an expanded genetic code, enabling efficient and precise manufacturing of antibody chemical conjugates, expanding the potential use of IgGl in medical treatments.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Oncology
Donatella Treppiedi, Anna Maria Barbieri, Genesio Di Muro, Giusy Marra, Federica Mangili, Rosa Catalano, Emanuela Esposito, Emanuele Ferrante, Andreea Liliana Serban, Marco Locatelli, Andrea Gerardo Lania, Anna Spada, Maura Arosio, Erika Peverelli, Giovanna Mantovani
Summary: Cushing's Disease is a rare and severe endocrine disorder caused by an ACTH-secreting pituitary tumor. Recent research has identified somatic mutations in the USP8 and USP48 genes in a subset of patients, with a novel USP8 variant found in one patient. Functional studies suggest that this somatic variant may play a role in the pathogenesis of ACTH-secreting tumors, expanding our understanding of the genetic landscape of Cushing's Disease.
Article
Biochemistry & Molecular Biology
Monika Gudowska-Sawczuk, Anna Moniuszko-Malinowska, Sara Paczek, Katarzyna Guziejko, Monika Chorazy, Barbara Mroczko
Summary: The aim of this study was to assess the synthesis of kappa and lambda free light chains (FLCs) in the serum of patients with COVID-19. The findings showed elevated levels of FLCs in COVID-19 patients and vaccinated individuals, and a correlation between FLCs and specific anti-SARS-CoV-2 antibodies and IL-6. Therefore, serum FLCs levels may serve as predictive markers for COVID-19.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Urology & Nephrology
Ji Zhang, Ziyuan Huang, Sishi Lin, Ya Hu, Yan Liang, Wenxian Qiu, Bo Chen, Chaosheng Chen
Summary: Patients with IgAN-lambda have higher levels of serum fibrinogen compared to patients with IgAN, and there are differences in immunofluorescence and pathological features. Furthermore, the prognosis of IgAN-lambda patients is worse, which is associated with light chain lambda restriction in the mesangial deposits, systemic inflammation, and crescent formation.
KIDNEY INTERNATIONAL REPORTS
(2022)
Article
Pathology
Huijuan Wu, Vincenzo L'Imperio, Mattia Rossi, Meghan E. Kapp, Paisit Paueksakon
Summary: This study compared the clinical manifestations, histologic findings, and clinical significance between AL-κ and AL-λ types of kidney AL amyloidosis. It found that AL-κ type had more severe amyloid deposition, higher serum creatinine level, indicating a worse prognosis and providing an important reference for clinical management.
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chunxin Wang, Mengjie Wang, Yan Wang, Junqian Pan, Changjiao Sun, Zhanghua Zeng, Shuaikai Ren, Haixin Cui, Xiang Zhao
Summary: Safe and efficient pesticide formulations have attracted great attention in recent years. This study developed a novel hydrophilic nano-formulation using nanotechnology, which showed improved particle size uniformity and dispersion compared to conventional methods. The effects of preparation parameters on particle size and morphology were investigated and the performance of the nano-formulation was evaluated.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Linchun Xu, Yongzhong Su
Summary: Immunoglobulin light chain amyloidosis (AL) is a chronic plasma cell disorder characterized by FLC misfolding and amyloid deposition, classified into non-hyperdiploidy and hyperdiploidy subtypes with distinct treatment responses and prognostic outcomes based on cytogenetic patterns. Other genetic factors, such as specific immunoglobulin light chain germline genes and somatic mutations, also contribute to amyloid formation in AL.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2021)
Article
Hematology
Ting Zhou, Constance M. Yuan, Kathryn Lurain, Clarissa Rous, Linda Weaver, Mark Raffeld, Maryalice Stetler-Stevenson, Thomas S. Uldrick, Armando C. Filie, Stefania Pittaluga, Elaine S. Jaffe, Vickie Marshall, Kyle Moore, Denise Whitby, Ramya Ramaswami, Robert Yarchoan, Hao-Wei Wang
Summary: Detection of LRP by flow cytometry can serve as a valuable tool in diagnosing KSHV-MCD, and KSHV inflammatory cytokine syndrome with LRP in effusions may represent a liquid-form of KSHV-MCD.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Agriculture, Dairy & Animal Science
Dapeng Yang, Ligang Yuan, Xiaojie Ma, Yumei Qi, Shaoyu Cheng, Yong Zhang
Summary: This study found that the expression of lambda light chains (lambda-LCs) significantly increased in the epididymis of cryptorchid Bactrian camels, and there were also structural changes in the epididymis and testis. These findings provide clues for further research on immunological infertility in cryptorchid Bactrian camels.
REPRODUCTION IN DOMESTIC ANIMALS
(2023)
Article
Oncology
Madeleine B. Hopson, Divaya Bhutani, Shawn Sarkaria, Mathew S. Maurer, Jan M. Griffin, Markus Mapara, Suzanne Lentzsch, Rajshekhar Chakraborty
Summary: The study found that different light chain (LC) isotypes in patients with AL amyloidosis can affect clinical features, but their impact on survival rates is uncertain.
LEUKEMIA & LYMPHOMA
(2022)
Article
Immunology
Sheng-Hsuan Wang, Bai-Jiun Kuo, Tzu-Chuan Ho, Shu-Wen Wan, Ko-Lun Yen, Po-Hui Huang, Oscar Guey Chuen Perng, Po-Lin Chen, Yu-Wen Chien, Yu-Chih Lo
Summary: This study found that dengue patients have elevated levels of serum FLCs, which are associated with disease severity. The study suggests that λ-FLCs can serve as serum markers for identifying and classifying dengue disease. Additionally, the study reveals that the elevation of serum λ-FLCs is mediated through NS3 protease-mediated antibody cleavage.
Article
Cell Biology
Prashanthi Dharanipragada, Nita Parekh
Summary: In this study, the genetics of diffuse large B-cell lymphoma (DLBCL) pathogenesis were investigated. Genetic variations were analyzed across different DLBCL subtypes, revealing distinct variation profiles and suggesting the need for novel patient stratification methods. The findings also provided insights into potential precision treatments for DLBCL.
Article
Hematology
Aneta Mikulasova, Cody Ashby, Ruslana G. Tytarenko, Pingping Qu, Adam Rosenthal, Judith A. Dent, Katie R. Ryan, Michael A. Bauer, Christopher P. Wardell, Antje Hoering, Konstantinos Mavrommatis, Matthew Trotter, Shayu Deshpande, Shmuel Yaccoby, Erming Tian, Jonathan Keats, Daniel Auclair, Graham H. Jackson, Faith E. Davies, Anjan Thakurta, Gareth J. Morgan, Brian A. Walker
Article
Oncology
Juan-Jose Garces, Michal Simicek, Marco Vicari, Lucie Brozova, Leire Burgos, Renata Bezdekova, Diego Alignani, Maria-Jose Calasanz, Katerina Growkova, Ibai Goicoechea, Xabier Agirre, Ludek Pour, Felipe Prosper, Rafael Rios, Joaquin Martinez-Lopez, Pamela Millacoy, Luis Palomera, Rafael Del Orbe, Albert Perez-Montana, Sonia Garate, Laura Blanco, Marta Lasa, Patricia Maiso, Juan Flores-Montero, Luzalba Sanoja-Flores, Zuzana Chyra, Alexander Vdovin, Tereza Sevcikova, Tomas Jelinek, Cirino Botta, Halima El Omri, Jonathan Keats, Alberto Orfao, Roman Hajek, Jesus F. San-Miguel, Bruno Paiva
Article
Oncology
Surbhi Sidana, Daniel P. Larson, Patricia T. Greipp, Rong He, Ellen D. McPhail, Angela Dispenzieri, David L. Murray, Surendra Dasari, Stephen M. Ansell, Eli Muchtar, Wilson I. Gonsalves, Taxiarchis V. Kourelis, Marina Ramirez-Alvarado, Prashant Kapoor, S. Vincent Rajkumar, Martha Q. Lacy, Francis K. Buadi, Nelson Leung, Robert A. Kyle, Shaji K. Kumar, Rebecca L. King, Morie A. Gertz
Article
Oncology
Torri L. Jordan, Khansaa Maar, Keely R. Redhage, Pinaki Misra, Luis M. Blancas-Mejia, Christopher J. Dick, Jonathan S. Wall, Angela Williams, Allan B. Dietz, Andre J. van Wijnen, Yi Lin, Marina Ramirez-Alvarado
Letter
Oncology
Linda B. Baughn, Zhuo Li, Kathryn Pearce, Celine M. Vachon, Mei-Yin Polley, Jonathan Keats, Eran Elhaik, Michael Baird, Terry Therneau, James R. Cerhan, P. Leif Bergsagel, Angela Dispenzieri, S. Vincent Rajkumar, Yan W. Asmann, Shaji Kumar
BLOOD CANCER JOURNAL
(2020)
Letter
Oncology
Luke Mountjoy, Sinto Sebastian, Tania Jain, Talal Hilal, Miguel Gonzalez-Velez, Marlene Girardo, Greg Ahmann, Jeremy Larsen, Leif Bergsagel, Rafael Fonseca
Article
Oncology
Joseph Longo, Petr Smirnov, Zhihua Li, Emily Branchard, Jenna E. van Leeuwen, Jonathan D. Licht, Benjamin Haibe-Kains, David W. Andrews, Jonathan J. Keats, Trevor J. Pugh, Suzanne Trudel, Linda Z. Penn
Summary: This study revealed that t(4;14)-positive multiple myeloma cells depend on the mevalonate (MVA) pathway for survival and are sensitive to statin treatment. Statins induce apoptosis in t(4;14)-positive cells and synergize with bortezomib to enhance anti-tumor activity.
Article
Medicine, General & Internal
Linda B. Baughn, Neeraj Sharma, Eran Elhaik, Aleksandar Sekulic, Alan H. Bryce, Rafael Fonseca
MAYO CLINIC PROCEEDINGS
(2020)
Article
Hematology
Vikas A. Gupta, Benjamin G. Barwick, Shannon M. Matulis, Ryosuke Shirasaki, David L. Jaye, Jonathan J. Keats, Benjamin Oberlton, Nisha S. Joseph, Craig C. Hofmeister, Leonard T. Heffner, Madhav Dhodapkar, Ajay K. Nooka, Sagar Lonial, Constantine S. Mitsiades, Jonathan L. Kaufman, Lawrence H. Boise
Summary: This study found that Venetoclax sensitivity is closely associated with the expression of B-cell genes and genomic features identified in transposase-accessible chromatin sequencing, and there are potential novel biomarkers associated with Venetoclax sensitivity.
Review
Oncology
Krisstina Gowin, Sheri Skerget, Jonathan J. Keats, Joseph Mikhael, Andrew J. Cowan
Summary: Plasma cell leukemia, whether primary or secondary, is a rare and aggressive blood disorder with poor survival rates despite effective therapies. Recent molecular studies using gene expression profiling and whole exome sequencing have provided new insights into the disease, potentially leading to improved prognosis and treatment strategies.
Article
Multidisciplinary Sciences
Sherry Bhalla, David T. Melnekoff, Adolfo Aleman, Violetta Leshchenko, Paula Restrepo, Jonathan Keats, Kenan Onel, Jeffrey R. Sawyer, Deepu Madduri, Joshua Richter, Shambavi Richard, Ajai Chari, Hearn Jay Cho, Joel T. Dudley, Sundar Jagannath, Alessandro Lagana, Samir Parekh
Summary: MM-PSN is the first multiomics patient similarity network for multiple myeloma, accurately dissecting the genetic and molecular landscape of the disease and identifying 12 distinct patient subgroups. These subgroups provide important information for patient prognosis and clinical management.
Article
Oncology
Sandeep S. Voleti, Rahma Warsame, Carolyn Mead-Harvey, Sikander Ailawadhi, Atul Jain, Rafael Fonseca, Joan M. Griffin, Nandita Khera
Summary: This study presents a standardized approach to describe the prevalence and predictors of financial hardship (FH) in cancer patients and examines its association with survival. It highlights the need for further research to develop care pathways for patients at high risk of poor financial and clinical outcomes.
JCO ONCOLOGY PRACTICE
(2022)
Review
Oncology
Rafael Fonseca, Diana Tran, Alyshia Laidlaw, Emily Rosta, Manvir Rai, Joana Duran, Eric M. Ammann
Summary: This systematic literature review aimed to understand the impact of disease progression, line of therapy, and clinical response on health-related quality of life in multiple myeloma patients. Through multiple rounds of screening, 41 studies were included, indicating that disease progression and increasing lines of therapy were associated with worsened patient HRQoL, while increasing depth of response was associated with improved patient HRQoL.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Review
Oncology
Timothy M. Schmidt, Rafael Fonseca, Saad Z. Usmani
Summary: +1q chromosome gain is common in multiple myeloma, often seen as a poor prognostic marker but not uniformly adopted as high-risk. Controversy exists regarding its importance, with many genes at the 1q21 locus proposed to cause resistance to therapy.
BLOOD CANCER JOURNAL
(2021)
Article
Oncology
Rafael Fonseca, May Hagiwara, Sumeet Panjabi, Emre Yucel, Jacqueline Buchanan, Thomas Delea
Summary: The impact of disease progression on healthcare resource utilization and costs among multiple myeloma patients who have undergone stem cell transplant and systemic anti-myeloma therapy is significant.
BLOOD CANCER JOURNAL
(2021)