Edgar E Robles, Ye Jin, Padhraic Smyth, Richard H Scheuermann, Jack D Bui, Huan-You Wang, Jean Oak, Yu Qian
MOTIVATION: Precise identification of cancer cells in patient samples is essential for accurate diagnosis and clinical monitoring but has been a significant challenge in machine learning approaches for cancer precision medicine. In most scenarios, training data are only available with disease annotation at the subject or sample level. Traditional approaches separate the classification process into multiple steps that are optimized independently. Recent methods either focus on predicting sample-level diagnosis without identifying individual pathologic cells or are less effective for identifying heterogeneous cancer cell phenotypes...
September 26, 2023: Bioinformatics
Hongxia Chen, Yunpeng Bai, Michihiro Kobayashi, Shiyu Xiao, Sergio Barajas, Wenjie Cai, Sisi Chen, Jinmin Miao, Frederick Nguele Meke, Chonghua Yao, Yuxia Yang, Katherine Strube, Odelia Satchivi, Jianmin Sun, Lars Ronnstrand, James M Croop, H Scott Boswell, Yuzhi Jia, Huiping Liu, Loretta S Li, Jessica K Altman, Elizabeth A Eklund, Madina Sukhanova, Peng Ji, Wei Tong, Hamid Band, Danny T Huang, Leonidas C Platanias, Zhong-Yin Zhang, Yan Liu
Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival. PRL2 enhances oncogenic KIT signaling in leukemia cells, promoting their proliferation and survival. We found that PRL2 dephosphorylates CBL at tyrosine 371 and inhibits its activity toward KIT, leading to decreased KIT ubiquitination and enhanced AKT and ERK signaling in leukemia cells...
September 27, 2023: Molecular Cancer Research: MCR
Daria Frank, Pradeep Kumar Patnana, Jan Vorwerk, Lianghao Mao, Lavanya Mokada Gopal, Noelle Jung, Thorben Hennig, Leo Ruhnke, Joris Maximillian Frenz, Maithreyan Kuppusamy, Robert J Autry, Lanying Wei, Kaiyan Sun, Helal Ahmed, Axel Künstner, Hauke Busch, Heiko Müller, Stephan Hutter, Gregor Hoermann, Longlong Liu, Xiaoqing Xie, Yahya Al-Matary, Subbaiah Chary Nimmagadda, Fiorella Charles Cano, Michael Heuser, Felicitas R Thol, Gudrun Göhring, Doris Steinemann, Jürgen Thomale, Theo Leitner, Anja Fischer, Roland Rad, Christoph Röllig, Heidi Altmann, Desiree Kunadt, Wolfgang E Berdel, Jana Hüve, Felix Neumann, Jürgen Klingauf, Virginie Calderon, Bertram Opalka, Ulrich Dührsen, Frank Rosenbauer, Martin Dugas, Julian Varghese, H Christian H Reinhardt, Nikolas von Bubnoff, Tarik Möröy, Georg Lenz, Aarif M N Batcha, Marianna Giorgi, Murugan Selvam, Eunice S Wang, Shannon K McWeeney, Jeffrey W Tyner, Friedrich Stölzel, Matthias Mann, Ashok Kumar Jayavelu, Cyrus Khandanpour
Growth Factor Independence 1 (GFI1) is a DNA-binding transcription factor and a key regulator of haematopoiesis. GFI1-36N is a germline variant causing a change of serine (S) to asparagine (N) at position 36. We previously reported that the GFI1-36N allele has a prevalence of 10-15% among patients with acute myeloid leukemia (AML) and 5-7% among healthy Caucasians and promotes the development of this disease. Using a multi-omics approach, we show here that GFI1-36N expression is associated with increased frequencies of chromosomal aberrations, mutational burden and mutational signatures in both murine and human AML and impedes homologous recombination-directed (HR) DNA repair in leukemic cells...
September 26, 2023: Blood
Søren T Bønløkke, Christian Fenger-Eriksen, Hans Beier Ommen, Anne-Mette Hvas
Thrombosis and bleeding are significant contributors to morbidity and mortality in patients with hematological cancer, and the impact of altered fibrinolysis on bleeding and thrombosis risk is poorly understood. In this prospective cohort study, we investigated the dynamics of fibrinolysis in hematological cancer patients. Fibrinolysis was investigated prior to treatment and three months after treatment initiation. A dynamic clot formation and lysis assay was performed beyond the measurement of plasminogen activator inhibitor 1, tissue- and urokinase-type plasminogen activators (tPA and uPA), plasmin-antiplasmin complexes (PAP), α-2-antiplasmin activity, and plasminogen activity...
September 27, 2023: Blood Advances
Mia Sanda, Daniel Dunea, Stefania Iordache, Alin Pohoata, Ana-Maria Glod-Lendvai, Ion Onutu
This study examines the levels of benzene and the potential health impact during three years of continuous monitoring (2019-2021), including the COVID-lockdown period from 2020 in a city that is an important Romanian center for petroleum refining and associated product manufacturing. The dataset contains benzene, toluene, NOx, PM10 concentrations, and meteorological factors monitored by six automatic stations from the national network of which four are in the city and two outside. Special attention was given to the benzene dynamics to establish patterns related to the health impact and leukemia...
September 2, 2023: Toxics
Afke Ekels, Simone Oerlemans, Sanne B Schagen, Djamila E Issa, Noortje Thielen, Marten R Nijziel, Marjolein W M van der Poel, Lindy P J Arts, Eduardus F M Posthuma, Lonneke V van de Poll-Franse
PURPOSE: To investigate the proportion of patients with lymphoma with persistent clinically relevant cognitive impairment, and its relation to  treatment, fatigue, and psychological distress. METHODS: Patients with diffuse-large-B-cell-lymphoma (DLBCL), follicular-lymphoma (FL), and chronic-lymphocytic-leukemia (CLL)/small-lymphocytic-lymphoma (SLL), diagnosed between 2004-2010 or 2015-2019, were followed up to 8 years post-diagnosis. Sociodemographic and clinical data were obtained from the Netherlands Cancer Registry and the Population-based HAematological Registry for Observational Studies...
September 27, 2023: Journal of Cancer Survivorship: Research and Practice
Esra Aydemir, İsmail İshak Arslan, Ahmet Hakan Görkay
The use of nonionizing electromagnetic fields (EMFs) has attracted interest in cancer research during the past few decades due to its noninvasive therapeutic successes in the treatment of cancer. Some epidemiological studies suggest that there may be a link between exposure to EMF and developing malignancies (such as leukemia and gliomas) or neurodegenerative diseases since EMF has a variety of biological effects such as altering reactive oxygen species (ROS)-regulated pathways. EMF exposure, however, has the potential to cause cancer cells to undergo a period of regulated cell death...
September 28, 2023: Advances in Experimental Medicine and Biology
Shuang Xia, Jia-Ting Ma, Emanuel Raschi, Rui Ma, Bi-Kui Zhang, Linna Guo, Yoshihiro Noguchi, Mayur Sarangdhar, Hui Gong, Miao Yan
BACKGROUND AND OBJECTIVE: Although tumor lysis syndrome was reported with obinutuzumab and rituximab, the association with CD20 monoclonal antibodies for chronic lymphocytic leukemia is unclear. METHODS: A disproportionality analysis was conducted to investigate the link between CD20 monoclonal antibodies and tumor lysis syndrome by accounting for known confounders and comparing with other anticancer drugs, using data from the US Food and Drug Administration Adverse Event Reporting System...
September 27, 2023: Clinical Drug Investigation
Hannah Vanrusselt, Dieudonné Buh Kum, Valerio Taverniti, Cheng Liu, Abel Acosta Sanchez, Nikky Corthout, Sebastian Munck, Thomas F Baumert, Leonid Beigelman, Lawrence M Blatt, Julian A Symons, Jerome Deval, Pierre Raboisson, Eloi R Verrier, Andreas Jekle, Sandrine Vendeville, Yannick Debing
Capsid assembly modulators (CAMs) are a novel class of therapeutic small molecules with the potential to address the continued global challenge posed by chronic hepatitis B (CHB). Class A CAMs (CAM-As) are particularly attractive because they induce loss of hepatitis B virus (HBV)-infected hepatocytes in animal models. All CAM-As described to date are heteroaryldihydropyrimidines (HAPs) which come with several drawbacks. Here, we report on the first non-HAP CAM-As ALG-005398 and ALG-005863 and provide a detailed in vitro intracellular characterization...
September 27, 2023: Journal of Virology
Sandra Clara Soares, Louis J D Roux, Ana Rita Castro, Cristina Cardoso Silva, Rita Rodrigues, Viviana M P Macho, Fátima Silva, Céu Costa
Acute lymphocytic leukemia (ALL) is the most frequent form of all childhood leukemias, mostly affecting children between 2 and 4 years old. Oral symptoms, such as mouth ulcers, mucositis, xerostomia, Herpes or Candidiasis, gingival enlargement and bleeding, petechiae, erythema, mucosal pallor and atrophic glossitis, are very common symptoms of ALL and can be early signs of the disease. Secondary and tertiary complications, a direct effect of chemo and radiotherapy, are associated with more severe bleeding, higher susceptibility to infections, ulcerations, inflammation of the mucous membranes, osteoradionecrosis, xerostomia, taste alterations, trismus, carious lesions and dental abnormalities...
August 24, 2023: Hematology Reports
Aida Zeckanovic, Philipp Fuchs, Philip Heesen, Nicole Bodmer, Maria Otth, Katrin Scheinemann
Adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) have significantly worse outcomes than their younger counterparts. Current treatment guidelines rely mostly on non-randomized retrospective studies. We performed a systematic review of studies published within the last 15 years comparing pediatric-inspired regimens (PIR) versus adult-type regimens or performing an age-stratified analysis of outcomes in the AYA population. Due to the heterogeneity of data, a meta-analysis was not possible...
September 20, 2023: Current Oncology
John Paul Yun, Philip Q Ding, Aastha Dolley, Winson Y Cheung
The management of myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) is limited and remains an unmet need. Decitabine/cedazuridine (DEC-C, ASTX727) is Canada's first and only approved oral hypomethylating agent for MDS and CMML. We characterized the real-world use of DEC-C through a Canadian compassionate use program. Demographic and clinical data from 769 patients enrolled in Taiho Pharma Canada's Patient Support Program were collected and analyzed. These patients represent a collection period from 10 November 2020 to 31 August 2022 with a median age of 76 years...
August 30, 2023: Current Oncology
Katja Seipel, Scarlett Kohler, Ulrike Bacher, Thomas Pabst
Targeting the molecular chaperone HSP90 and the anti-apoptotic proteins MCL1 and BCL2 may be a promising novel approach in the treatment of acute myeloid leukemia (AML). The HSP90 inhibitor PU-H71, MCL1 inhibitor S63845, and BCL2 inhibitor venetoclax were assessed as single agents and in combination for their ability to induce apoptosis and cell death in leukemic cells. AML cells represented all major morphologic and molecular subtypes including FLT3-ITD and TP53 mutant AML cell lines and a variety of patient-derived AML cells...
August 23, 2023: Current Issues in Molecular Biology
Yue Zhou, Li Wang, Li-Rong Sun, Li Zhang, Hong-Mei Wang, Xi-Ting Liu, Fan Yang, Ke-Liang Wu, Yu-Li Liang, Bei-Bei Zhao, Yong Zhuang, Jin-Qiu Fu, Chao Song, Yun Li, Ling-Zhen Wang, Hui-Juan Xu, Yan Gu, John van den Anker, Xiu-Li Ju, Xiao-Fan Zhu, Wei Zhao
Continuous 6-mercaptopurine (6-MP) dose titration is necessary because of its narrow therapeutic index and frequently encountered dose-limiting hematopoietic toxicity. However, evidence-based guidelines for gene-based 6-MP dosing have not been established for Chinese children with acute lymphoblastic leukemia (ALL). This multicenter, randomized, open-label, active-controlled clinical trial randomly assigned Chinese children with low- or intermediate-risk ALL in a 1:1 ratio to receive TPMT-NUDT15 gene-based dosing of 6-MP (N = 44, 10 to 50 mg/m2 /day) or standard dosing (N = 44, 50 mg/m2 /day) during maintenance therapy...
September 27, 2023: Clinical Pharmacology and Therapeutics
Fadi G Haddad, Nicholas J Short
No abstract text is available yet for this article.
September 27, 2023: American Journal of Hematology
Senthil Velan Bhoopalan, Shruthi Suryaprakash, Akshay Sharma, Marcin W Wlodarski
Diamond-Blackfan anemia (DBA) is one of the most common inherited causes of bone marrow failure in children. DBA typically presents with isolated erythroid hypoplasia and anemia in infants. Congenital anomalies are seen in 50% of the patients. Over time, many patients experience panhematopoietic defects resulting in immunodeficiency and multilineage hematopoietic cytopenias. Additionally, DBA is associated with increased risk of myelodysplastic syndrome, acute myeloid leukemia and solid organ cancers. As a prototypical ribosomopathy, DBA is caused by heterozygous loss-of-function mutations or deletions in over 20 ribosomal protein genes, with RPS19 being involved in 25% of patients...
2023: Frontiers in Oncology
Cindy Wu, Deepa Dongarwar, Samer Al Hadidi
Plasma cell leukemia (PCL) is a rare, aggressive subtype of multiple myeloma (MM) with a poor prognosis. Prior studies have shown that racial disparities affect MM patients in various ways, which may affect patients' outcomes. In this study, we aimed to investigate racial differences in hospitalization outcomes for PCL using Nationwide Inpatient Sample data. Overall, hospitalization rates for PCL tended to decrease over the past decade. Among hospitalized patients with a primary diagnosis of PCL, there was no statistically significant association between race/ethnicity and hospitalization rates, between NH-White patients and NH-Black patients (OR 1...
2023: Clinical hematology international
Constantine S Tam, Nicole Lamanna, Susan M O'Brien, Lugui Qiu, Keri Yang, Gisoo Barnes, Ken Wu, Tommi Salmi, Jennifer R Brown
OBJECTIVE: The purpose of this analysis was to assess health-related quality of life (HRQoL) in patients treated with zanubrutinib and ibrutinib in the ALPINE trial (NCT03734016). METHODS: HRQoL was measured by the EORTC QLQ-C30 and EQ-5D-5L at baseline, cycle 1, and every third cycle until end of treatment. Key patient-reported outcome (PRO) endpoints included global health status (GHS), physical and role functioning, as well as symptoms of fatigue, pain, diarrhea, and nausea/vomiting...
September 27, 2023: Current Medical Research and Opinion
Paolo Ghia, Gisoo Barnes, Keri Yang, Constantine S Tam, Tadeusz Robak, Jennifer R Brown, Brad S Kahl, Tian Tian, Andy Szeto, Jason C Paik, Mazyar Shadman
OBJECTIVE: Zanubrutinib is a highly selective, next-generation Bruton's tyrosine kinase inhibitor. In the phase 3 SEQUOIA trial (NCT03336333), treatment with zanubrutinib resulted in significantly improved progression-free survival compared to bendamustine plus rituximab (BR) in adult patients with treatment-naïve chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) without del(17p). The current analysis compared the effects of zanubrutinib versus BR on patients' health-related quality of life (HRQoL)...
September 27, 2023: Current Medical Research and Opinion
Mingyang Wang, Haixiao Zhang, Xinhui Zheng, Jia Liu, Jiali Wang, Yigeng Cao, Xiaoyu Zhang, Rongli Zhang, Xin Chen, Weihua Zhai, Qiaoling Ma, Jialin Wei, Yong Huang, Donglin Yang, Yi He, Aiming Pang, Sizhou Feng, Mingzhe Han, Erlie Jiang
Autologous hematopoietic stem cell transplantation (auto-HSCT), matched sibling donor HSCT (MSD-HSCT), and alternative donor HSCT (AD-HSCT) are viable post-remission treatment options for acute myeloid leukemia (AML). A total of 283 de novo favorable- and intermediate-risk AML patients, based on the ELN 2022 criteria, in first complete remission were initially included for propensity score matching. Following the matching process, 126 patients were selected for further analysis, with 42 patients in each of the auto-HSCT, MSD-HSCT, and AD-HSCT groups...
September 26, 2023: Hematological Oncology
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