Article
Oncology
Miguel Quijada-Alamo, Claudia Perez-Carretero, Maria Hernandez-Sanchez, Ana-Eugenia Rodriguez-Vicente, Ana-Belen Herrero, Jesus-Maria Hernandez-Sanchez, Marta Martin-Izquierdo, Sandra Santos-Minguez, Monica Del Rey, Teresa Gonzalez, Araceli Rubio-Martinez, Alfonso Garcia de Coca, Julio Davila-Valls, Jose-Angel Hernandez-Rivas, Helen Parker, Jonathan C. Strefford, Rocio Benito, Jose-Luis Ordonez, Jesus-Maria Hernandez-Rivas
Summary: Our study found that concurrent biallelic ATM and TP53 loss is mutually exclusive in CLL, while monoallelic del(11q) and TP53 alterations significantly co-occur in a subset of patients with poor prognosis. CRISPR/Cas9-edited CLL cell lines revealed that combined del(11q) and TP53 mutations provide clonal advantage, whereas CLL cells with biallelic ATM and TP53 loss fail to compete in xenotransplants. Furthermore, CLL cell lines with del(11q) and TP53 mutations show partial responses to B cell receptor signaling inhibitors, indicating potential benefit from ATR inhibition.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Hikaru Sakamoto, Koji Ando, Yoshitaka Imaizumi, Hiroyuki Mishima, Akira Kinoshita, Yuji Kobayashi, Hideaki Kitanosono, Takeharu Kato, Yasushi Sawayama, Shinya Sato, Tomoko Hata, Masahiro Nakashima, Koh-Ichiro Yoshiura, Yasushi Miyazaki
Summary: The study found that inhibiting cyclin-dependent protein kinase 9 (CDK9) and regulating super-enhancers (SE) tumor-specific gene expression have therapeutic potential for adult T-cell leukemia/lymphoma (ATL). The CDK9 inhibitor, Alvocidib, demonstrated anti-ATL activity by inhibiting SE-mediated IRF4 expression and inhibiting ATL cell proliferation. The study also revealed the promising therapeutic efficacy of Alvocidib against ATL and its mode of action.
Article
Medicine, Research & Experimental
Qing Huang, Kathleen L. Deering, Qing Harshaw, Lori A. Leslie
Summary: This study found that first-line single-agent ibrutinib therapy was associated with significantly longer time to next treatment than CIT regimens in high-risk CLL patients. The results support the use of ibrutinib in high-risk patients.
ADVANCES IN THERAPY
(2022)
Article
Oncology
Yi-Xin Zou, Han-Ning Tang, Jing Zhang, Xiao-Lu Tang, Shu-Chao Qin, Yi Xia, Hua-Yuan Zhu, Chun Qiao, Li Wang, Lei Fan, Wei Xu, Jian-Yong Li, Yi Miao
Summary: The 11q deletion is a common cytogenetic aberration in CLL patients, with a relatively low prevalence but unfavorable prognosis for untreated patients. Two nomograms were established to accurately predict the prognosis of untreated CLL patients.
TRANSLATIONAL ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Nawar Maher, Samir Mouhssine, Bassam Francis Matti, Alaa Fadhil Alwan, Gianluca Gaidano
Summary: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Chemoimmunotherapy (CIT) was the commonest option for CLL treatment, but resistance to CIT has led to the use of targeted pathway inhibitors such as BTK and BCL2 inhibitors. However, acquired genetic lesions can cause resistance to these inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Miguel Quijada-Alamo, Maria Hernandez-Sanchez, Ana-Eugenia Rodriguez-Vicente, Claudia Perez-Carretero, Alberto Rodriguez-Sanchez, Marta Martin-Izquierdo, Veronica Alonso-Perez, Ignacio Garcia-Tunon, Jose Maria Bastida, Maria Jesus Vidal-Mancenido, Josefina Galende, Carlos Aguilar, Jose Antonio Queizan, Isabel Gonzalez-Gascon Y Marin, Jose-Angel Hernandez-Rivas, Rocio Benito, Jose Luis Ordonez, Jesus-Maria Hernandez-Rivas
Summary: This study demonstrates that monoallelic deletion of BIRC3 in del(11q) CLL cells promotes activation of non-canonical NF-kappa B signaling, with further enhancement of this effect in cells with biallelic BIRC3 loss. Additionally, BIRC3 mutations accelerate leukemic progression in CLL, highlighting the biological mechanisms underlying disease progression in patients with del(11q) CLL harboring BIRC3 deletion and mutation.
BLOOD CANCER JOURNAL
(2021)
Article
Oncology
Salem H. Alshemmari, Abdulaziz Hamdah, Ramesh Pandita, Anita Kunhikrishnan
Summary: CLL is a rare hematological malignancy in the Middle East. The cohort in this study is younger with less del13q expression, but similar rates of IGHV mutations were observed. Median progression-free survival (PFS) was 178 months for the entire cohort, with a median OS of 203 months.
Article
Oncology
Remi Letestu, Abdelmalek Dahmani, Marouane Boubaya, Lucile Baseggio, Lydia Campos, Bernard Chatelain, Agathe Debliquis, Bernard Drenou, Marie-Christine Jacob, Eric Legac, Magali Le Garff-Tavernier, Anne-Catherine Lhoumeau, Claire Quiney, Nelly Robillard, Michel Ticchioni, Carmen Aanei, Sandrine Katsahian, Roselyne Delepine, Sandrine Vaudaux, Valerie Rouille, Marie-Christine Bene, Caroline Dartigeas, Eric van den Neste, Stephane Lepretre, Pierre Feugier, Guillaume Cartron, Veronique Leblond, Vincent Levy, Florence Cymbalista
Summary: High-sensitivity MRD assessment in patients with chronic lymphocytic leukemia can provide additional prognostic information, with low-level positive MRD in blood associated with longer progression-free survival, but not in bone marrow.
Article
Biophysics
Nico Gagelmann, Diderik-Jan Eikema, Liesbeth C. de Wreede, Alessandro Rambaldi, Simona Iacobelli, Linda Koster, Denis Caillot, Didier Blaise, Peter Rememyi, Claude-Eric Bulabois, Jakob Passweg, Xavier Leleu, Samo Zver, Guido Kobbe, Per Ljungman, Patrice Chevallier, Mark Ringhoffer, Murray Martin, Urpu Salmenniemi, Xavier Poire, Stig Lenhoff, Pietro Pioltelli, Nicola Mordini, Michel Delforge, Laurent Garderet, Stefan Schoenland, Ibrahim Yakoub-Agha, Nicolaus Kroeger
Summary: The study found that for patients with t(4;14), tandem autologous and tandem autologous/reduced-intensity allogeneic transplantation were associated with better progression-free survival (PFS), while for patients with del(17p), there was no significant difference in outcome.
BONE MARROW TRANSPLANTATION
(2021)
Article
Oncology
Youngwoo Jeon, Duk-Hwan Yang, Suk-Joong Oh, Jin-Hee Park, Jung-Ah Kim, Sung-Young Kim, Chul-Won Choi, Won-Sik Lee, In-Ho Kim, Yeung-Chul Mun, Gi June Min, Ki-Seong Eom, Seok-Goo Cho
Summary: This study evaluated the prophylactic effectiveness of pegfilgrastim in reducing neutropenia and febrile neutropenia in CLL patients undergoing R-FC chemotherapy. The results showed that prophylactic pegfilgrastim significantly reduced the incidence of neutropenia and febrile neutropenia, as well as the risk of treatment interruption and treatment-related mortality.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Andriana Valkama, Sandra Vorimo, Timo A. Kumpula, Hannele Raesaenen, Eeva-Riitta Savolainen, Katri Pylkas, Tuomo Mantere
Summary: The standard-of-care cytogenetic analysis of chronic lymphocytic leukemia (CLL) is currently based on the fluorescence in situ hybridization (FISH) technique, which offers limited genomic information. Recent studies have shown the potential of optical genome mapping (OGM) as a cytogenetic tool for hematological malignancies. In this study, we evaluated the concordance between OGM and standard-of-care FISH in 18 CLL samples. The results were fully concordant, and OGM revealed additional genomic alterations and complex karyotypes that were undetectable by FISH. Based on these findings, OGM could be used as a first-tier cytogenetic test for CLL.
Article
Oncology
Qinlu Li, Shugang Xing, Heng Zhang, Xiao Mao, Min Xiao, Ying Wang
Summary: IGH-t is not uncommon among Chinese CLL patients, with diverse partner genes and distinct gene mutational profiles compared to the non-IGH-t group. Identifying IGH-t and its partner genes may refine risk stratification and enhance accurate management in CLL patients.
FRONTIERS IN ONCOLOGY
(2022)
Article
Health Care Sciences & Services
Yuan Hong, Xichuang Chen, Yuanquan Hong, Xingfang Xiao, Yan Wang, Xiaohong You, Jingyi Mi, Tao Zhou, Panpan Zheng, Zhihu Huang
Summary: This study performed a long-term economic evaluation and found that the first-line treatment with IB is more cost-effective compared to the first-line BE plus RI treatment strategy for older patients with CLL without the del(17p)/TP53 mutation in China.
BMC HEALTH SERVICES RESEARCH
(2023)
Article
Medicine, General & Internal
Lori A. Leslie, Nilesh Gangan, Hiangkiat Tan, Qing Huang
Summary: This study evaluated the trend in cytogenetic/molecular testing rate in CLL and assessed the clinical and economic burden of first-line treatment with CIT in high-risk patients. The results showed that high-risk CLL patients treated with 1 L CIT had poorer clinical and economic outcomes compared to non-high risk patients. The study also highlighted the need for improvement in genetic risk assessment.
CURRENT MEDICAL RESEARCH AND OPINION
(2022)
Article
Medicine, General & Internal
Martin Andres, Anita Feller, Volker Arndt
Summary: There is no significant trend in age-adjusted incidence rates for chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL) patients in Switzerland. However, age-standardised survival has improved over time, particularly in younger age groups, with statistically significant improvement seen in patients aged 65-74 years. Males have higher incidence rates, mortality rates, and shorter survival compared to females.
SWISS MEDICAL WEEKLY
(2021)
Article
Oncology
Junan Li, Avinash K. Persaud, Jasmine A. Johnson, Dougkas W. Sborov, Mitch A. Phelps, Craig C. Hofmeister, Ming J. Poi
Summary: This study investigated the association of select single nucleotide polymorphisms in the SLC22A3 gene with clinical outcomes in multiple myeloma patients. The results suggested that a specific genotype was associated with altered melphalan transport and an increased risk of severe oral mucositis.
ANTICANCER RESEARCH
(2022)
Article
Hematology
Swagata Goswami, Rajeswaran Mani, Jessica Nunes, Chi-Ling Chiang, Kevan Zapolnik, Eileen Hu, Frank Frissora, Xiaokui Mo, Logan A. Walker, Pearlly Yan, Ralf Bundschuh, Larry Beaver, Raymond Devine, Yo-Ting Tsai, Ann Ventura, Zhiliang Xie, Min Chen, Rosa Lapalombella, Alison Walker, Alice Mims, Karilyn Larkin, Nicole Grieselhuber, Chad Bennett, Mitch Phelps, Erin Hertlein, Gregory Behbehani, Sumithira Vasu, John C. Byrd, Natarajan Muthusamy
Summary: This study reveals that silencing of protein phosphatase 2A (PP2A) directly blocks differentiation in acute myeloid leukemia (AML). Activation of PP2A regulates cell cycle and transcriptional regulators, thereby modulating terminal myeloid differentiation. This finding highlights the potential therapeutic targeting of the PP2A/c-Myc/p21 axis in malignancies with dysregulated maturation fate.
Article
Oncology
Yizhen Guo, Lai Wei, Sandip H. Patel, Gabrielle Lopez, Madison Grogan, Mingjia Li, Tyler Haddad, Andrew Johns, Latha P. Ganesan, Yiping Yang, Daniel J. Spakowicz, Peter G. Shields, Kai He, Erin M. Bertino, Gregory A. Otterson, David P. Carbone, Carolyn Presley, Samuel K. Kulp, Thomas A. Mace, Christopher C. Coss, Mitch A. Phelps, Dwight H. Owen
Summary: Serum albumin and early albumin decrease are significantly associated with overall survival in patients with advanced non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitor (ICI) therapy. This study suggests that albumin changes may serve as potential biomarkers to predict treatment outcomes and warrant further investigation.
CLINICAL LUNG CANCER
(2022)
Article
Plant Sciences
Leslie N. Aldrich, Joanna E. Burdette, Esperanza Carcache de Blanco, Christopher C. Coss, Alessandra S. Eustaquio, James R. Fuchs, A. Douglas Kinghorn, Amanda MacFarlane, Brittney K. Mize, Nicholas H. Oberlies, Jimmy Orjala, Cedric J. Pearce, Mitch A. Phelps, Liva Harinantenaina Rakotondraibe, Yulin Ren, Djaja Doel Soejarto, Brent R. Stockwell, Jack C. Yalowich, Xiaoli Zhang
Summary: Research progress in the discovery of potential anticancer agents from various organisms has been summarized. Lead compounds with structural diversity have been obtained, and potential antitumor activities have been demonstrated. Further investigations are warranted for promising lead compounds.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Chemistry, Multidisciplinary
Christopher R. Lucas, Patrick D. Halley, Amjad A. Chowdury, Bonnie K. Harrington, Larry Beaver, Rosa Lapalombella, Amy J. Johnson, Erin K. Hertlein, Mitch A. Phelps, John C. Byrd, Carlos E. Castro
Summary: The study demonstrates that DNA origami (DO) nanotechnology can be used to construct precise nanostructures capable of functionalization and has a wide range of biomedical applications. DO structures distribute well systemically, eliciting a gradually diminishing mild pro-inflammatory response, while being non-toxic.
Article
Biochemistry & Molecular Biology
Justin Thomas, Molly A. Torok, Kriti Agrawal, Timothy Pfau, Trang T. Vu, Justin Lyberger, Hsiaochi Chang, Alyssa Marie M. Castillo, Min Chen, Bryan Remaily, Kyeongmin Kim, Zhiliang Xie, Mary E. Dillhoff, Samuel K. Kulp, Gregory K. Behbehani, Zobeida Cruz-Monserrate, Latha P. Ganesan, Dwight H. Owen, Mitch A. Phelps, Christopher C. Coss, Thomas A. Mace
Summary: The neonatal Fc receptor (FcRn) is responsible for recycling antibodies and albumin in the body. However, little is known about its expression in circulating immune cells. In this study, FcRn expression was found to be elevated in immune cells of pancreatic ductal adenocarcinoma (PDAC) patients and mice with PDAC. These findings may contribute to understanding the mechanisms behind poor efficacy of antibody immunotherapies in PDAC patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Oncology
Swagata Goswami, Chi-Ling Chiang, Kevan Zapolnik, Jessica Nunes, Ann Ventura, Xiaokui Mo, Zhiliang Xie, L. James Lee, Sivasubramanian Baskar, Christoph Rader, John C. Byrd, Mitch Phelps, Bhavana Bhatnagar, Natarajan Muthusamy
Article
Dermatology
Dylan L. Burroughs, Gwendolen Lorch, Yizhen Guo, Kasey Hill, Eric L. Schroeder, Lynette K. Cole, Mitch A. Phelps
Summary: This study aimed to define the noncompartmental pharmacokinetic parameters of intravenous mycophenolate mofetil (MMF) and its downstream metabolites in healthy horses. The results showed that horses biotransform MMF into mycophenolic acid (MPA), MPA phenol glucuronide (MPAG), MPA acyl glucuronide (AcMPAG), and MPA phenol glucoside (MPG).
VETERINARY DERMATOLOGY
(2023)
Article
Oncology
Junan LI, Yu kyoung Cho, Douglas W. Sborov, Mitch A. Phelps, Craig C. Hofmeister, Ming J. Poi
Summary: This study aimed to evaluate the potential impacts of CYP3A4*1B and CYP3A5*3 gene variations on the pharmacokinetic properties of melphalan and clinical outcomes in multiple myeloma patients. The results showed that CYP3A4*1B/*1B and CYP3A5*3/*3 carriers had shorter median progression-free survival time and higher maximum melphalan plasma concentration. Through yet-to-be-identified mechanisms, CYP3A4*1B/*1B and CYP3A5*3/*3 variations might influence melphalan therapy in MM patients.
CANCER GENOMICS & PROTEOMICS
(2023)
Article
Hematology
Chaitra Ujjani, Ted A. Gooley, Stephen E. Spurgeon, Deborah M. Stephens, Catherine Lai, Catherine M. Broome, Susan O'Brien, Haiying Zhu, Kerry J. Laing, Allison M. Winter, Georgios Pongas, Alexander L. Greninger, David M. Koelle, Tanya Siddiqi, Matthew S. Davids, Kerry A. Rogers, Alexey V. Danilov, Amy Sperling, Brian Tu, Tyler Sorensen, Kelsey Launchbury, Carlissa J. Burrow, Genesis Quezada, Joshua A. Hill, Mazyar Shadman, Philip A. Thompson
Summary: This study aimed to analyze the immune responses of patients with chronic lymphocytic leukemia (CLL) to the COVID-19 vaccine, including T-cell responses, and the impact of CLL therapeutics. The study found that patients receiving B-cell-directed therapy were less likely to have immune conversion. Additionally, the immune response persisted at 6 months, and administration of booster vaccinations enhanced the immune response. However, caution should be exercised as newer variants emerge and escape vaccine-induced immunity.
Review
Pharmacology & Pharmacy
Kyeongmin Kim, Mitch A. A. Phelps
Summary: Daratumumab is a fully human monoclonal antibody used for the treatment of multiple myeloma and light-chain amyloidosis. It works by targeting CD38 and has demonstrated anti-myeloma activity through various mechanisms. The dosing schedule and exposure to daratumumab are important factors for its efficacy, but disease and patient characteristics do not significantly affect its exposure or response.
CLINICAL PHARMACOKINETICS
(2023)
Article
Oncology
Ryan D. Gentzler, Liza C. Villaruz, John C. Rhee, Bethany Horton, Joseph Mock, Michael Hanley, Kyeongmin Kim, Michelle A. Rudek, Mitch A. Phelps, Michael A. Carducci, Richard Piekarz, Kwon-Sik Park, Timothy N. Bullock, Charles M. Rudin
Summary: This study evaluated the safety of combining the HDAC inhibitor entinostat with standard of care chemotherapy and immunotherapy in patients with small cell lung cancer. The results showed that the addition of entinostat resulted in early onset and severe neutropenia and thrombocytopenia, indicating that further exploration of this combination therapy is not recommended.
Meeting Abstract
Obstetrics & Gynecology
Kara M. Rood, Marwan Ma'ayeh, Mahmoud Abdelwahab, Melanie Paglione, Nicole Abbott, Kasey Hill, Janet Guo, Kyeongmin Kim, Douglas Kniss, Mitch A. Phelps, Maged M. Costantine
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
(2023)
Meeting Abstract
Obstetrics & Gynecology
Jennifer L. Grasch, Chelsea Cobe, Kristen L. Benninger, Erin M. Cleary, Mitch A. Phelps, Maged M. Costantine, Kara M. Rood
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
(2023)
Meeting Abstract
Oncology
Ola A. Elgamal, Sandip Vibhute, Sydney Fobare, Abeera Mehmood, Mariah L. Johnson, Jean Truxall, Emily Stahl, Bridget Carmichael, Shelley J. Orwick, Ramasamy Santhanam, Kasey Hill, Susheela Tridandapani, Christopher C. Coss, Alice S. Mims, Karilyn T. Larkin, Mitch A. Phelps, Sharyn D. Baker, Alex Sparreboom, Thomas E. Goodwin, Gerard Hilinski, Chad E. Bennett, Erin Hertlein, John C. Byrd
