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JOURNAL ARTICLE
Terese Knoppers, Cassandra E Haley, Sarah Bouhouita-Guermech, Julie Hagan, Jacqueline Bradbury-Jost, Samuel Alarie, Marie Cosquer, Ma'n H Zawati
BACKGROUND: Acute myeloid leukemia (AML), a rapidly progressing cancer of the blood and bone marrow, is the most common and fatal type of adult leukemia. Therapeutic web portals have great potential to facilitate AML research advances and improve health outcomes by increasing the availability of data, the speed and reach of new knowledge, and the communication between researchers and clinicians in the field. However, there is a need for stakeholder research regarding their optimal features, utility, and implementation...
2024: PloS One
#2
JOURNAL ARTICLE
Joaquin Garcia-Solorio, Juan Carlos Núñez-Enriquez, Marco Jiménez-Olivares, Janet Flores-Lujano, Fernanda Flores-Espino, Carolina Molina-Garay, Alejandra Cervera, Diana Casique-Aguirre, José Gabriel Peñaloza-Gonzalez, Ma Del Rocío Baños-Lara, Ángel García-Soto, César Alejandro Galván-Díaz, Alberto Olaya-Vargas, Hilario Flores Aguilar, Minerva Mata-Rocha, Miguel Ángel Garrido-Hernández, Juan Carlos Solís-Poblano, Nuria Citlalli Luna-Silva, Lena Sarahi Cano-Cuapio, Pierre Mitchel Aristil-Chery, Fernando Herrera-Quezada, Karol Carrillo-Sanchez, Anallely Muñoz-Rivas, Luis Leonardo Flores-Lagunes, Elvia Cristina Mendoza-Caamal, Beatriz Eugenia Villegas-Torres, Vincent González-Osnaya, Elva Jiménez-Hernández, José Refugio Torres-Nava, Jorge Alfonso Martín-Trejo, María de Lourdes Gutiérrez-Rivera, Rosa Martha Espinosa-Elizondo, Laura Elizabeth Merino-Pasaye, María Luisa Pérez-Saldívar, Silvia Jiménez-Morales, Everardo Curiel-Quesada, Haydeé Rosas-Vargas, Juan Manuel Mejía-Arangure, Carmen Alaez-Verson
BACKGROUND: Recurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5 , CDKN2A/2B , or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL...
2024: Frontiers in Oncology
#3
JOURNAL ARTICLE
Nandita Noronha, Chantal Durette, Maxime Cahuzac, Bianca E Silva, Justine Courtois, Juliette Humeau, Allan Sauvat, Marie-Pierre Hardy, Krystel Vincent, Jean-Philippe Laverdure, Joël Lanoix, Frédéric Baron, Pierre Thibault, Claude Perreault, Gregory Ehx
The hypomethylating agent 5-azacytidine (AZA) is the first-line treatment for AML patients unfit for intensive chemotherapy. The effect of AZA results in part from T-cell cytotoxic responses against MHC-I-associated peptides (MAPs) deriving from hypermethylated genomic regions such as cancer-testis antigens (CTAs), or endogenous retroelements (EREs). However, evidence supporting higher ERE MAPs presentation after AZA treatment is lacking. Therefore, using proteogenomics, we examined the impact of AZA on the repertoire of MAPs and their source transcripts...
April 16, 2024: Leukemia
#4
REVIEW
Jennifer R Brown
Our understanding of risk factors for the development of chronic lymphocytic leukemia (CLL) is still incomplete and includes genetic and environmental factors. CLL is one of the most familial of all cancers, yet common high-penetrance risk alleles have not been identified. Genome-wide association studies have identified many common variants with low relative risks, whereas exome-wide rare variant analysis has implicated ATM in CLL causation. Environmental factors have also been challenging to identify given the limited understanding of the relevant time period of exposure relative to diagnosis, and the inability to quantify past exposures...
April 2024: Journal of the National Comprehensive Cancer Network: JNCCN
#5
JOURNAL ARTICLE
Huiying Sun, Yangyang Xie, Xiaoyan Wu, Wenting Hu, Xiaoxiao Chen, Kefei Wu, Han Wang, Shuang Zhao, Qiaoqiao Shi, Xiang Wang, Bowen Cui, Wenyan Wu, Rongrong Fan, Jianan Rao, Ronghua Wang, Ying Wang, Ying Zhong, Hui Yu, Binbing S Zhou, Shuhong Shen, Yu Liu
Circular RNAs (circRNAs) arise from precursor mRNA processing through back-splicing and have been increasingly recognized for their functions in various cancers including acute myeloid leukemia (AML). However, the prognostic implications of circRNA in AML remain unclear. We conducted a comprehensive genome-wide analysis of circRNAs using RNA-seq data in pediatric AML. We revealed a group of circRNAs associated with inferior outcomes, exerting effects on cancer-related pathways. Several of these circRNAs were transcribed directly from genes with established functions in AML, such as circRUNX1, circWHSC1, and circFLT3...
April 13, 2024: Cancer Letters
#6
JOURNAL ARTICLE
Zhen Lu, Qian Lai, Zhi-Feng Li, Meng-Ya Zhong, Yue-Long Jiang, Li-Ying Feng, Jie Zha, Jing-Wei Yao, Yin Li, Xian-Ming Deng, Bing Xu
OBJECTIVE: In B-cell acute lymphoblastic leukemia (B-ALL), current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50% of cases, underscoring the urgent need for new therapeutic regimens for this patient population. The present study aimed to determine whether HZX-02-059, a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) and tubulin, is lethal to B-ALL cells and is a potential therapeutic for B-ALL patients...
April 15, 2024: Current Medical Science
#7
REVIEW
Mischa Y L Vervoordeldonk, Paul J Hengeveld, Mark-David Levin, Anton W Langerak
The molecular landscape of chronic lymphocytic leukemia (CLL) has been extensively characterized, and various potent prognostic biomarkers were discovered. The genetic composition of the B-cell receptor (BCR) immunoglobulin (IG) was shown to be especially powerful for discerning indolent from aggressive disease at diagnosis. Classification based on the IG heavy chain variable gene (IGHV) somatic hypermutation status is routinely applied. Additionally, BCR IGH stereotypy has been implicated to improve risk stratification, through characterization of subsets with consistent clinical profiles...
April 15, 2024: Leukemia & Lymphoma
#8
JOURNAL ARTICLE
Guangrong Qin, Jin Dai, Sylvia Chien, Timothy J Martins, Brenda Loera, Quy H Nguyen, Melanie L Oakes, Bahar Tercan, Boris Aguilar, Lauren Hagen, Jeannine McCune, Richard Gelinas, Raymond J Monnat, Ilya Shmulevich, Pamela S Becker
PURPOSE: The inherent genetic heterogeneity of acute myeloid leukemia (AML) has challenged the development of precise and effective therapies. The objective of this study was to elucidate the genomic basis of drug resistance or sensitivity, identify signatures for drug response prediction, and provide resources to the research community. EXPERIMENTAL DESIGN: We performed targeted sequencing, high-throughput drug screening, and single-cell genomic profiling on leukemia cell samples derived from patients with AML...
April 15, 2024: Clinical Cancer Research
#9
JOURNAL ARTICLE
Waad Almuatasem Mohieldeen, Albara Ahmed, Yousif Mohammed Elmosaad, Rania Saad Suliman, Abdulaziz Alfahed, Ahmed Hjazi, Humood Al Shmrany, Nora Hakami, Mohammed Ageeli Hakami, Alhomidi Almotiri, Hisham Ali Waggiallah
BACKGROUND: A genetic polymorphism that causes abnormal folate metabolism may lead to genomic instability and increase susceptibility to malignancies such as Acute Lymphoblastic leukemia (ALL). The purpose of this research is to identify methylene tetrahydrofolate reductase (MTHFR C677T) (NCBI ID: 4524) mutation in ALL patients. METHODS: The study was a descriptive case-control hospital-based study with one hundred Sudanese participants divided equally into fifty (50) Sudanese ALL diagnosed patients as cases and fifty (50) Sudanese individuals as controls...
October 2023: Reports of Biochemistry & Molecular Biology
#10
JOURNAL ARTICLE
Xinghao Yu, Yiyin Chen, Jia Chen, Yi Fan, Huimin Lu, Depei Wu, Yang Xu
BACKGROUND: To study the shared genetic structure between autoimmune diseases and B-cell acute lymphoblastic leukemia (B-ALL) and identify the shared risk loci and genes and genetic mechanisms involved. METHODS: Based on large-scale genome-wide association study (GWAS) summary-level data sets, we observed genetic overlaps between autoimmune diseases and B-ALL, and cross-trait pleiotropic analysis was performed to detect shared pleiotropic loci and genes. A series of functional annotation and tissue-specific analysis were performed to determine the influence of pleiotropic genes...
April 15, 2024: BMC Medicine
#11
JOURNAL ARTICLE
Shiyi Pan, Qinghua Cai, Yiqiong Wei, Haifeng Tang, Yuping Zhang, Wei Zhou, Tingfen Deng, Wenjian Mo, Shunqing Wang, Caixia Wang, Cunte Chen
BACKGROUND: Inducible co-stimulatory factor (ICOS) has a dual role: activating cytotoxic T cells against tumors or exacerbating immunosuppression of regulatory T cells (Tregs) to participate in immune evasion. However, the correlation between ICOS and its co-expression with inhibitory immune checkpoints (IICs) and prognosis in acute myeloid leukemia (AML) is little known. METHODS: The prognostic importance of ICOS and IICs in 62 bone marrow (BM) samples of de novo AML patients from our clinical center (GZFPH) was explored and then the RNA sequencing data of 155 AML patients from the Cancer Genome Atlas (TCGA) database was used for validation...
April 11, 2024: Immunobiology
#12
JOURNAL ARTICLE
Yaqi Zhao, A Douglas Laird, Kathryn G Roberts, Rolla L Yafawi, Hagop M Kantarjian, Daniel J DeAngelo, Matthias Stelljes, Michaela Liedtke, Wendy Stock, Nicola Gökbuget, Susan M O'Brien, Elias J Jabbour, Ryan D Cassaday, Melanie R Loyd, Scott R Olsen, Geoffrey A Neale, Xueli Liu, Erik Vandendries, Anjali S Advani, Charles G Mullighan
The phase 3 INO-VATE trial demonstrated higher rates of remission, measurable residual disease negativity, and improved overall survival for patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) who received inotuzumab ozogamicin (InO) vs standard of care chemotherapy (SC). Here we examined associations between genomic alterations and the efficacy of InO. Of 326 randomized patients, 91 (InO, n=43; SC, n=48) had samples evaluable for genomic analysis. The spectrum of gene fusions and other genomic alterations observed was comparable with prior studies of adult ALL...
March 26, 2024: Blood Advances
#13
JOURNAL ARTICLE
Yue Huang, Dapeng Chen, Yi Bai, Yamin Zhang, Zhiwen Zheng, Qingfeng Fu, Bocun Yi, Yuchen Jiang, Zhihong Zhang, Jianqiang Zhu
PURPOSE: Establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the mitotic S-phase adhesins acetylation and is responsible for bridging two sister chromatids. However, present ESCO2 cancer research is limited to a few cancers. No systematic pan-cancer analysis has been conducted to investigate its role in diagnosis, prognosis, and effector function. METHODS: We thoroughly examined the ESCO2 carcinogenesis in pan-cancer by combining public databases such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), UALCAN and Tumor Immune Single-cell Hub (TISCH)...
April 11, 2024: BMC Cancer
#14
JOURNAL ARTICLE
Eddy N de Boer, Vincent Vroom, Arjen J Scheper, Lennart F Johansson, Laura Bosscher, Nettie Rietema, Sabrina Z Commandeur-Jan, Nine V A M Knoers, Birgit Sikkema-Raddatz, Eva van den Berg, Cleo C van Diemen
Leukemias are genetically heterogeneous and diagnostics therefore includes various standard-of-care (SOC) techniques, including karyotyping, SNP-array and FISH. Optical genome mapping (OGM) may replace these as it detects different types of structural aberrations simultaneously and additionally detects much smaller aberrations (500 bp vs 5-10 Mb with karyotyping). However, its resolution may still be too low to define clinical relevance of aberrations when they are located between two OGM labels or when labels are not distinct enough...
April 12, 2024: Scientific Reports
#15
JOURNAL ARTICLE
Chenxu Xiao, Xiaochu Gu, Yu Feng, Jing Shen
INTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with poorly understood pathophysiology. Recent studies have highlighted systemic inflammation, especially the role of circulating inflammatory proteins, in ALS. METHODS: This study investigates the potential causal link between these proteins and ALS. We employed a two-sample Mendelian Randomization(MR) approach, analyzing data from large-scale genome-wide association studies to explore the relationship between 91 circulating inflammatory proteins and ALS...
2024: Frontiers in Aging Neuroscience
#16
Yingying Shen, Junmin Cao, Tonglin Hu, Xiawan Yang, Yuechao Zhao, Yiping Shen, Baodong Ye, Yunsong Yu, Dijiong Wu
BACKGROUND: Carbapenem-resistant P. aeruginosa (CRPA) is a common hospital-acquired bacterium. It exhibits high resistance to many antibiotics, including ceftazidime/avibactam and cefteolozane/tazobactam . The presence of carbapenem-resistant genes and co-existence Klebsiella pneumoniae carbapenemase (KPC) and metallo-β-lactamases (MBLs) further inactivated all β-lactams. Understanding the resistance genes of CRPA can help in uncovering the resistance mechanism and guiding anti-infective treatment...
2024: Infection and Drug Resistance
#17
JOURNAL ARTICLE
Axel Künstner, Julian Schwarting, Hanno M Witte, Pengwei Xing, Veronica Bernard, Stephanie Stölting, Philipp Lohneis, Florian Janke, Maede Salehi, Xingqi Chen, Kathrin Kusch, Holger Sültmann, Emil Chteinberg, Anja Fischer, Reiner Siebert, Nikolas von Bubnoff, Hartmut Merz, Hauke Busch, Alfred C Feller, Niklas Gebauer
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) constitutes a rare and aggressive malignancy originating from plasmacytoid dendritic cells (pDCs) with a primarily cutaneous tropism followed by dissemination to the bone marrow and other organs. We conducted a genome-wide analysis of the tumor methylome in an extended cohort of 45 BPDCN patients supplemented by WES and RNA-seq as well as ATAC-seq on selected cases. We determined the BPDCN DNA methylation profile and observed a dramatic loss of DNA methylation during malignant transformation from early and mature DCs towards BPDCN...
April 10, 2024: Leukemia
#18
JOURNAL ARTICLE
Jiuwei Lu, Yiran Guo, Jiekai Yin, Jianbin Chen, Yinsheng Wang, Gang Greg Wang, Jikui Song
DNA methyltransferases DNMT3A- and DNMT3B-mediated DNA methylation critically regulate epigenomic and transcriptomic patterning during development. The hotspot DNMT3A mutations at the site of Arg822 (R882) promote polymerization, leading to aberrant DNA methylation that may contribute to the pathogenesis of acute myeloid leukemia (AML). However, the molecular basis underlying the mutation-induced functional misregulation of DNMT3A remains unclear. Here, we report the crystal structures of the DNMT3A methyltransferase domain, revealing a molecular basis for its oligomerization behavior distinct to DNMT3B, and the enhanced intermolecular contacts caused by the R882H or R882C mutation...
April 10, 2024: Nature Communications
#19
REVIEW
Magda Zanelli, Valentina Fragliasso, Giuseppe Gaetano Loscocco, Francesca Sanguedolce, Giuseppe Broggi, Maurizio Zizzo, Andrea Palicelli, Stefano Ricci, Elisa Ambrogi, Giovanni Martino, Sara Aversa, Francesca Coppa, Pietro Gentile, Fabrizio Gozzi, Rosario Caltabiano, Nektarios Koufopoulos, Aleksandra Asaturova, Luca Cimino, Alberto Cavazza, Giulio Fraternali Orcioni, Stefano Ascani
Myeloproliferative neoplasms (MPNs) are subdivided into Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) and Ph-negative MPNs. BCR::ABL1 translocation is essential for the development and diagnosis of CML; on the other hand, the majority of Ph-negative MPNs are characterized by generally mutually exclusive mutations of Janus kinase 2 ( JAK2 ), calreticulin ( CALR ), or thrombopoietin receptor/myeloproliferative leukemia ( MPL ). CALR mutations have been described essentially in JAK2 and MPL wild-type essential thrombocythemia and primary myelofibrosis...
2024: Frontiers in Cell and Developmental Biology
#20
REVIEW
Katarzyna Bugiel-Stabla, Chiara Agnoli, Aleksandra Pawlak
Estrogen receptors (ERs) are located in both healthy and neoplastic tissues. The type of estrogen receptor expressed varies depending on its location, tumor type, and species. Estrogen action is mediated by binding to ER and activating the transcriptional and signaling processes that result in the control of gene expression. There are two main types of estrogen receptors: ER alpha (ERα) and ER beta (ERβ). Both receptors are functionally different, they may act antagonistically and are distributed in different tissues but their structure is similar - as they are composed of 5 different domains: A/B, C, D, E, and F...
April 10, 2024: Veterinary Research Communications
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