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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
#2
REVIEW
Tariq Kewan, Maximillian Stahl, Jan Philipp Bewersdorf, Amer M Zeidan
PURPOSE OF REVIEW: Myelodysplastic syndromes/neoplasms (MDS) represent a diverse group of pathologically distinct diseases with varying prognoses and risks of leukemia progression. This review aims to discuss current treatment options for elderly patients with MDS, focusing on patients ineligible for intensive chemotherapy or allogenic hematopoietic stem cell transplantation (HSCT). The challenges associated with treatment in this population and emerging therapeutic prospects are also explored...
April 18, 2024: Current Hematologic Malignancy Reports
#3
JOURNAL ARTICLE
Hong Jia-Xin, Xu Song'en, Zhang Wen-Qing, Liu Wei
Granulopoiesis is a highly ordered and precisely regulated process in which hematopoietic-related transcription factors play crucial roles. These transcription factors form complex regulatory networks through interactions with their co-factors or with each other, and anomalies in these networks can lead to the onset of leukemia. While the structures and functions of dozens of transcription factors involved in this process have been extensively studied, research on the regulatory relationships between these factors remains relatively limited...
April 20, 2024: Yi Chuan, Hereditas
#4
Deepali Bhalla, Sunil Sati, Donald Basel, Vijender Karody
Stüve-Wiedemann syndrome (SWS) is a rare autosomal recessive disorder that is characterized by bowing of long bones, dysautonomia, temperature dysregulation, swallowing and feeding difficulties, and frequent respiratory infections. Respiratory distress and hyperthermic events are the leading causes of early neonatal death, and most patients are not expected to survive past infancy. Here, we report on the survival of a 5-year-old male with SWS, discussing his case presentation, providing a brief clinical course, and discussing the outcome...
2024: Frontiers in Pediatrics
#5
JOURNAL ARTICLE
Xue Zhong, Nagesh Peddada, James J Moresco, Jianhui Wang, Yiao Jiang, Jonathan J Rios, Eva Marie Y Moresco, Jin Huk Choi, Bruce Beutler
In a genetic screen, we identified two viable missense alleles of the essential gene Midnolin (Midn) that were associated with reductions in peripheral B cells. Causation was confirmed in mice with targeted deletion of four of six MIDN protein isoforms. MIDN was expressed predominantly in lymphocytes where it augmented proteasome activity. We showed that purified MIDN directly stimulated 26S proteasome activity in vitro in a manner dependent on the ubiquitin-like domain and a C-terminal region. MIDN-deficient B cells displayed aberrant activation of the IRE-1/XBP-1 pathway of the unfolded protein response...
June 3, 2024: Journal of Experimental Medicine
#6
JOURNAL ARTICLE
Xinrong Xiang, Zhengyi Dai, Baozhu Luo, Ninglin Zhao, Song Liu, Jing Sui, Jiasheng Huang, Yuanzheng Zhou, Jinlong Gu, Jiangnan Zhang, Tao Yang, Rui Bao, Youfu Luo
The activation of Homo sapiens Casein lysing protease P (HsClpP) by a chemical or genetic strategy has been proved to be a new potential therapy in acute myeloid leukemia (AML). However, limited efficacy has been achieved with classic agonist imipridone ONC201 . Here, a novel class of HsClpP agonists is designed and synthesized using a ring-opening strategy based on the lead compound 1 reported in our previous study. Among these novel scaffold agonists, compound 7k exhibited remarkably enhanced proteolytic activity of HsClpP (EC50 = 0...
April 15, 2024: Journal of Medicinal Chemistry
#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
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
#10
REVIEW
Hee Sue Park
Recently, the International Consensus Classification (ICC) and the 5th edition of the World Health Organization classification (WHO2022) introduced diagnostically similar yet distinct approaches, which has resulted in practical confusion. This review compares these classification systems for acute myeloid leukemia (AML), building up on the revised 4th edition of WHO (WHO2016). Both classifications retain recurrent genetic abnormalities as a primary consideration. However, they differ in terms of blast threshold...
April 15, 2024: Blood Research
#11
JOURNAL ARTICLE
Husam B R Alabed, Roberto Maria Pellegrino, Sandra Buratta, Anair Graciela Lema Fernandez, Roberta La Starza, Lorena Urbanelli, Cristina Mecucci, Carla Emiliani, Paolo Gorello
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive tumor mainly affecting children and adolescents. It is driven by multiple genetic mutations that together define the leukemic phenotype. Interestingly, based on genetic alterations and/or deregulated expression, at least six genetic subgroups have been recognized. The TAL/LMO subgroup is one of the most represented genetic subgroups, characterizing 30-45% of pediatric T-ALL cases. The study of lipid and metabolic profiles is increasingly recognized as a valuable tool for comprehending the development and progression of tumors...
March 31, 2024: International Journal of Molecular Sciences
#12
REVIEW
Marika Kulczycka, Kamila Derlatka, Justyna Tasior, Maja Sygacz, Monika Lejman, Joanna Zawitkowska
Infant acute lymphoblastic leukemia (Infant ALL) is a kind of pediatric ALL, diagnosed in children under 1 year of age and accounts for less than 5% of pediatric ALL. In the infant ALL group, two subtypes can be distinguished: KMT2A -rearranged ALL, known as a more difficult to cure form and KMT2A - non-rearranged ALL with better survival outcomes. As infants with ALL have lesser treatment outcomes compared to older children, it is pivotal to provide novel treatment approaches. Progress in the development of molecularly targeted therapies and immunotherapy presents exciting opportunities for potential improvement...
March 27, 2024: International Journal of Molecular Sciences
#13
JOURNAL ARTICLE
Chiara Camoglio, Jihane Balla, Paola Fadda, Simona Dedoni
Oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) are endogenous lipids that act as agonists of the peroxisome proliferator-activated receptor α (PPARα). Recently, an interest in the role of these lipids in malignant tumors has emerged. Nevertheless, the effects of OEA and PEA on human neuroblastoma cells are still not documented. Type I interferons (IFNs) are immunomodulatory cytokines endowed with antiviral and anti-proliferative actions and are used in the treatment of various pathologies such as different cancer forms (i...
April 2, 2024: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
#14
JOURNAL ARTICLE
Ga-Young Song, Hyeon-Jong Kim, TaeHyung Kim, Seo-Yeon Ahn, Sung-Hoon Jung, Mihee Kim, Deok-Hwan Yang, Je-Jung Lee, Mi Yeon Kim, June-Won Cheong, Chul Won Jung, Jun Ho Jang, Hee- Je Kim, Joon Ho Moon, Sang Kyun Sohn, Jong-Ho Won, Seong Kyu Park, Sung-Hyun Kim, Chang Kyun Choi, Hyeoung-Joon Kim, Jae-Sook Ahn, Dennis Dong Hwan Kim
This study aimed to validate the 2022 European LeukemiaNet (ELN) risk stratification for acute myeloid leukemia (AML). A total of 624 newly diagnosed AML patients from 1998 to 2014 were included in the analysis. Genetic profiling was conducted using targeted deep sequencing of 45 genes based on recurrent driver mutations. In total, 134 (21.5%) patients had their risk classification reassessed according to the 2022 ELN risk stratification. Among those initially classified as having a favorable risk in 2017 (n = 218), 31 and 3 patients were reclassified as having intermediate risk or adverse risk, respectively...
April 12, 2024: Scientific Reports
#15
JOURNAL ARTICLE
Jia-Yuan Zhang, Zhang-Song Yan, Xiu-Juan Sun, Yong-Ze Liu, Yan-Ke Yin, Ming-Huan Su, Qiu-Ling Li, Ying-Chang Mi, Da-Peng Li
Objectives This study aimed to identify the association between lactate dehydrogenase (LDH) levels and 30-day mortality in patients with intracranial hemorrhage (ICH) with acute leukemia during the induction phase. Methods This cohort study included patients with acute leukemia with ICH during induction. We evaluated serum LDH levels upon admission. Multivariable Cox regression analyzed the LDH 30-day mortality association. Interaction and stratified analyses based on factors like age, sex, albumin, white blood cell count, hemoglobin level, and platelet count were conducted...
June 2024: Global medical genetics
#16
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
#17
JOURNAL ARTICLE
Sai Huang, Peng Chen, Lu Wang, Lingmin Xu, Nan Wang, Fei Li, Liping Dou, Daihong Liu
BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy whose prognosis is associated with several biomarkers. Decitabine, a deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibitor, combined with cytarabine, aclarubicin hydrochloride, and granulocyte colony-stimulating factor (DCAG), has been used in patients newly diagnosed with AML. This regimen has been especially used in older and fragile patients who are immunocompromised or have co-morbidities, as well as those with specific gene mutations...
April 2024: Cancer Pathog Ther
#18
JOURNAL ARTICLE
Robert Schauner, Jordan Cress, Changjin Hong, David Wald, Parameswaran Ramakrishnan
INTRODUCTION: Acute myeloid leukemia (AML) is the most common acute leukemia in adults with an overall poor prognosis and high relapse rate. Multiple factors including genetic abnormalities, differentiation defects and altered cellular metabolism contribute to AML development and progression. Though the roles of oxidative phosphorylation and glycolysis are defined in AML, the role of the hexosamine biosynthetic pathway (HBP), which regulates the O-GlcNAcylation of cytoplasmic and nuclear proteins, remains poorly defined...
2024: Frontiers in Immunology
#19
REVIEW
Harry Fruchtman, Zachary M Avigan, Julian A Waksal, Nicole Brennan, John O Mascarenhas
The emergence of next generation sequencing and widespread use of mutational profiling in acute myeloid leukemia (AML) has broadened our understanding of the heterogeneous molecular basis of the disease. Since genetic sequencing has become a standard practice, several driver mutations have been identified. Accordingly, novel targeted therapeutic agents have been developed and are now approved for the treatment of subsets of patients that carry mutations in FLT3, IDH1, and IDH2 [1, 2]. The emergence of these novel agents in AML offers patients a new modality of therapy, and shifts treatment paradigms toward individualized medicine...
April 10, 2024: Leukemia
#20
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
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