Wen-Yan Cheng, Jian-Feng Li, Yong-Mei Zhu, Xiang-Jie Lin, Li-Jun Wen, Fan Zhang, Yu-Liang Zhang, Ming Zhao, Hai Fang, Sheng-Yue Wang, Xiao-Jing Lin, Niu Qiao, Wei Yin, Jia-Nan Zhang, Yu-Ting Dai, Lu Jiang, Xiao-Jian Sun, Yi Xu, Tong-Tong Zhang, Su-Ning Chen, Hong-Hu Zhu, Zhu Chen, Jie Jin, De-Pei Wu, Yang Shen, Sai-Juan Chen
The current classification of acute myeloid leukemia (AML) relies largely on genomic alterations. Robust identification of clinically and biologically relevant molecular subtypes from nongenomic high-throughput sequencing data remains challenging. We established the largest multicenter AML cohort (n = 655) in China, with all patients subjected to RNA sequencing (RNA-Seq) and 619 (94.5%) to targeted or whole-exome sequencing (TES/WES). Based on an enhanced consensus clustering, eight stable gene expression subgroups (G1-G8) with unique clinical and biological significance were identified, including two unreported (G5 and G8) and three redefined ones (G4, G6, and G7)...
December 6, 2022: Proceedings of the National Academy of Sciences of the United States of America
Curtis A Lachowiez, Nicola Long, Jennifer N Saultz, Arpita Gandhi, Laura F Newell, Brandon Hayes-Lattin, Richard T Maziarz, Jessica Leonard, Daniel Bottomly, Shannon K McWeeney, Jennifer Dunlap, Richard D Press, Gabrielle Meyers, Ronan Swords, Rachel Cook, Jeffrey W Tyner, Brian J Druker, Elie Traer
Risk stratification in acute myeloid leukemia (AML) remains principle for survival prognostication and treatment selection. The 2022 European LeukemiaNet (ELN) recommendations were recently published, with notable updates to risk group assignment. The complexity of risk stratification and comparative outcomes between the 2022 and 2017 ELN guidelines remains unknown. This comparative analysis evaluated outcomes between the 2017 and 2022 ELN criteria in patients enrolled within the multi-center Beat AML cohort...
November 28, 2022: Blood Advances
Robin Hallett, Ester Bonfill-Teixidor, Raffaella Iurlaro, Alexandra Arias, Swetha Raman, Peter E Bayliss, Olga Egorova, Almudena Neva-Alejo, Aj Robert McGray, Esther Lau, Alexandre Bosch, Melissa Beilschmidt, Dorothea Maetzel, Johan Fransson, Isabel Huber-Ruano, Judit Anido, Jean-Philippe Julien, Patricia A Giblin, Joan Seoane
PURPOSE: Leukemia inhibitory factor (LIF) is a multifunctional cytokine with numerous reported roles in cancer and is thought to drive tumor development and progression. Characterization of LIF and clinical-stage LIF inhibitors would increase our understanding of LIF as a therapeutic target. EXPERIMENTAL DESIGN: We first tested the association of LIF expression with transcript signatures representing multiple processes regulating tumor development and progression...
November 28, 2022: Clinical Cancer Research
Thomas Björk-Eriksson, Martina Boström, Ing-Liss Bryngelsson, Päivi M Lähteenmäki, Marianne Jarfelt, Marie Kalm, Daniel S Olsson
IMPORTANCE: Acute lymphoblastic leukemia (ALL) constitutes 20% to 30% of all pediatric cancers. The 5-year overall survival among pediatric patients with ALL in high-income countries such as Sweden is currently more than 90%, but long-term unselected nationwide mortality data and mortality data in relation to the general population are lacking. OBJECTIVE: To compare mortality between pediatric patients with ALL and the general population during a 30-year period in Sweden and to assess the incidence of ALL in Sweden...
November 1, 2022: JAMA Network Open
Shuancheng Zhang, Yucong Ma, Qianqian Zuo, Mengrui Liu, Zhifang Yu, Ying Sun, Cuimiao Song, Hongyan Sun, Guimin Hao, Bulang Gao, Huilan Du, Jingwei Chen
The effects of repeated controlled ovarian stimulation (COS) on the female reproductive system are still controversial. This study investigated the effects of repeated COS on the ovaries and uterus of mice and its possible mechanism. Female ICR (Institute of Cancer Research) mice were subjected to the COS using pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) for 1, 3, 5, and 7 cycles. Serum hormone levels, reactive oxidative stress (ROS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), total antioxidant capacity (T-AOC), and superoxide dismutase (SOD) in the mouse ovary and uterus were analyzed by ELISA...
November 28, 2022: Human Cell
Jian Liang-Fonseca, Klaus Geissler
In a retrospective study, we analyzed the prevalence of elevated C‑reactive protein (CRP) serum levels in 148 patients with chronic myelomonocytic leukemia (CMML), their potential prognostic impact, and potential correlations with laboratory features. Normal, up to 10-fold, and more than 10-fold elevated CRP levels were found in 18%, 59%, and 23% of CMML patients, respectively. Using the CRP cutoff value of 10 mg/L of the widely used Glasgow score, high CRP values were associated with inferior survival (13 vs...
November 28, 2022: Wiener Medizinische Wochenschrift
Daisuke Tomizawa
Acute lymphoblastic leukemia (ALL) in infants accounts for less than 5% of pediatric ALL and is biologically and clinically unique. Approximately 70% to 80% of cases present as an aggressive leukemia with KMT2A gene rearrangement (KMT2A-r), which is one of the most difficult-to-cure forms of pediatric leukemia. Owing to continuing global efforts through multicenter clinical trials since the mid-1990s, a standard of care for infant KMT2A-r ALL, including minimal residual disease-based risk stratifications, "hybrid chemotherapy" incorporating myeloid leukemia-like drugs (e...
November 28, 2022: International Journal of Hematology
Pavel Vodárek, Dominika Écsiová, Vladimíra Řezáčová, Ondřej Souček, Martin Šimkovič, Doris Vokurková, David Belada, Pavel Žák, Lukáš Smolej
BACKGROUND: In chronic lymphocytic leukemia (CLL), changes in the peripheral blood lymphocyte subsets play an important role in disease progression and infectious complications. The impact of chemoimmunotherapy (CIT) on these changes has not been extensively studied METHODS: We used multi-color flow cytometry, to prospectively measure absolute and relative numbers of CD4+ and CD8+ T-cells and their subsets in 45 patients with indolent untreated CLL, 86 patients indicated for first-line treatment, and 34 healthy controls...
November 28, 2022: Cancer Medicine
Pawel Dubiela, Piotr Humeniuk, Merima Bublin, Carine Metz-Favre, Sébastien Viel, Francoise Bienvenu, Christine Hafner, Gabrielle Pauli, Karin Hoffmann-Sommergruber
Vegetables provide important nutrients but can also induce allergic symptoms. Celery tuber allergy frequently occurs in Central European countries and can cause allergic reactions including fatal anaphylactic shocks. There is little information about allergen content in seeds. Therefore, we analyzed 2 patients with allergic reaction after remoulade sauce consumption who entered the clinic for a diagnostic work-up. The routine diagnostic included serum derived specific IgE testing by ImmunoCAP, ImmunoCAP ISAC, and skin prick tests (SPTs)...
November 2022: World Allergy Organization Journal
Franziska Schmidt, Miriam Erlacher, Charlotte Niemeyer, Dirk Reinhardt, Jan-Henning Klusmann
Twelve to 22% of pediatric acute myeloid leukemia (AML) patients present with hyperleukocytosis, which is one of the main risk factors of early death due to its clinical complications: leukostasis, causing pulmonary or central nervous system injuries, tumor lysis syndrome, and disseminated intravascular coagulation. Sorafenib is a multi-kinase inhibitor that blocks the Fms-Related Tyrosine Kinase 3 receptor ( FLT3 ) in AML patients with a FLT3 -internal tandem duplication ( FLT3 -ITD), leading to a reduction of proliferation...
2022: Frontiers in Pediatrics
Tadeusz Robak, Paweł Robak
Hairy cell leukemia (HCL) is a rare type of chronic lymphoid leukemia originating from a mature B lymphocyte. A diagnosis of HCL is based on cytology, confirmed by multiparametric flow cytometry (MFC) studies using anti-B-cell monoclonal antibodies, together with a panel of antibodies more specific to HCL, such as CD11c, CD25, CD103 and CD123. Recently, the BRAF V600E mutation has been described as a disease-defining genetic event. Measurable residual disease (MRD) is defined as the lowest level of HCL cells that can be detected accurately and reproducibly using validated methods; as MRD negativity is associated with high rates of durable complete response, by clearing MRD, the long-term outcome may be improved in patients with advanced HCL...
2022: Frontiers in Oncology
Qianru Zhan, Heyang Zhang, Boquan Wu, Naijin Zhang, Lijun Zhang
Acute leukemia is a common hematologic tumor with highly genetic heterogeneity, and many factors are involved in the pathogenesis and drug-resistance mechanism. Emerging evidence proves that E3 ubiquitin ligases participate in the acute leukemic signaling pathways via regulating substrates. This review summarized the E3 ligases which can affect the leukemic signal. It is worth noting that the abnormal signal is often caused by a deficiency or a mutation of the E3 ligases. In view of this phenomenon, we envisioned perspectives associated with targeted agonists of E3 ligases and proteolysis-targeting chimera technology...
2022: Frontiers in Physiology
Peifang Xiao, Jiaoyang Cai, Ju Gao, Wei Gao, Xianmin Guan, Alex Wing Kwan Leung, Yiying He, Yong Zhuang, Jinhua Chu, Xiaowen Zhai, Benquan Qi, Aiguo Liu, Liangchun Yang, Jiashi Zhu, Zheng Li, Xin Tian, Yao Xue, Li Hao, Xuedong Wu, Fen Zhou, Lingzhen Wang, Jingyan Tang, Shuhong Shen, Shaoyan Hu
BACKGROUND AND METHODS: The study evaluated prognostic factors associated with varicella-zoster virus (VZV) infection and mortality in children with acute lymphoblastic leukemia (ALL) using data from the multicenter Chinese Children's Cancer Group ALL-2015 trial. RESULTS: In total, 7,640 patients were recruited, and 138 cases of VZV infection were identified. The incidence of VZV infection was higher in patients aged ≥ 10 years (22.5%) and in patients with the E2A/PBX1 fusion gene (11...
2022: Frontiers in Cellular and Infection Microbiology
Chao Lin, Jia-Qi Xu, Gui-Chao Zhong, Hui Chen, Hong-Man Xue, Mo Yang, Chun Chen
BACKGROUND: Nicotinamide Adenine Dinucleotide (NAD) depletion is reported to be a potential treatment for B-cell Acute Lymphoblastic Leukemia (B-ALL), but the mechanism of NAD metabolism-related genes (NMRGs) in B-ALL relapse remains unclear. METHODS: Transcriptome data (GSE3912), and single-cell sequencing data (GSE130116) of B-ALL patients were downloaded from Gene Expression Omnibus (GEO) database. NMRGs were sourced from Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases...
2022: Frontiers in Immunology
Harjeet Singh, Samer A Srour, Denái R Milton, Jessica McCarty, Cuiping Dai, Mahmoud R Gaballa, Mariam Ammari, Simon Olivares, Helen Huls, Eleanor De Groot, David Marin, Demetrios Petropoulos, Amanda L Olson, Paolo Anderlini, Jin S Im, Issa Khouri, Chitra M Hosing, Katayoun Rezvani, Richard E Champlin, Elizabeth J Shpall, Laurence J N Cooper, Partow Kebriaei
Chimeric antigen receptor (CAR) T-cell therapy has emerged recently as a standard of care treatment for patients with relapsed or refractory acute lymphoblastic leukemia (ALL) and several subtypes of B-cell non-Hodgkin lymphoma (NHL). However, its use remains limited to highly specialized centers, given the complexity of its administration and its associated toxicities. We previously reported our experience in using a novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy in the peri-transplant setting, where it exhibited an excellent safety profile with encouraging survival outcomes...
2022: Frontiers in Immunology
Huiling Hu, Nannan Sun, Haiyan Du, Yuqing He, Kunyi Pan, Xiuli Liu, Xiaoxia Lu, Jie Wei, Mianmian Liao, Chaohui Duan
Previous studies have demonstrated that promyelocytic leukemia zinc finger protein (PLZF) promotes the expression of gluconeogenic genes and hepatic glucose output, which leads to hyperglycemia. However, the role played by PLZF in regulating lipid metabolism is not known. In this study, we aimed to examine the function of PLZF in regulating hepatic lipid and glucose homeostasis and the underlying mechanisms. The expression of PLZF was determined in different mouse models with regard to non-alcoholic fatty liver disease (NAFLD)...
2022: Frontiers in Pharmacology
Natharina Yolanda, Stefanus Gunawan, Max F J Mantik, Anjo J P Veerman
Juvenile myelomonocytic leukemia (JMML) is a rare hematopoietic malignancy in children, with an incidence of 1.2 per million children per year. At this moment, we present a case report and a brief literature review of JMML in a child, primarily focused on its applicability in low-middle income countries. A 3.5-year-old male was referred to our tertiary center due to pallor, enlarging abdomen and neck mass, recurrent fever, and chronic diarrhea. Initial laboratory workup showed hemoglobin of 6.4 g/dl, white blood cell of 315...
2022: Case Reports in Hematology
Shuting Chen, Qinchao Hu, Xiaoan Tao, Juan Xia, Tong Wu, Bin Cheng, Juan Wang
Retinoids, natural and synthetic derivatives of vitamin A, have many regulatory functions in human body, including regulating cellular proliferation, differentiation, apoptosis. Moreover, retinoids have been used successfully for the treatment of certain malignancies, especially acute promyelocytic leukemia (APL) in adults and neuroblastoma in children. However, retinoids have not yet been translated into effective systemic treatments for most solid cancers. Some recent studies have shown that retinoids promote tumorigenesis...
2022: Frontiers in Genetics
Akihiro Ohmoto, Shigeo Fuji, Satoshi Kohmo, Kaoruko Katsura
INTRODUCTION: Human T-cell leukemia virus type 1 (HTLV-I) associated bronchioloalveolar disorder (HABA) is a chronic and progressive bronchiolar/alveolar disorder related to HTLV-1 infection. Clinical knowledge and guidance are lacking for the diagnosis and management of this condition. AREAS COVERED: This work aimed to review the latest information and challenges regarding HABA diagnosis and treatment. EXPERT OPINION: HABA is an immune-mediated state induced by HTLV-1...
November 27, 2022: Expert Review of Anti-infective Therapy
Athanasios Bangeas, Efthymia Protonotariou, Emmanuel Hatzipantelis, Maria Palabougiouki, Maria Ioannidou, Lemonia Skoura, Assimina Galli-Tsinopoulou, Athanasios Tragiannidis
BACKGROUND/AIM: Infections are a major cause of morbidity and mortality in children with haematologic malignancies and solid tumors as well as those undergoing hematopoietic stem cell transplantation (HSCT). The purpose of our study was to record the epidemiological characteristics and outcomes of bacteremias, focusing on pathogens, as well as risk factors and mortality rates in patients of a pediatric hematology-oncology unit from Northern Greece. MATERIALS AND METHODS: A retrospective analysis was conducted, which included all positive blood cultures from pediatric hematology oncology patients aged from 1 to 16 years old admitted to the Pediatric and Adolescent Hematology Oncology Unit of AHEPA University Hospital of Thessaloniki between January 2014 and December 2018...
November 25, 2022: Cardiovascular & Hematological Agents in Medicinal Chemistry
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