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JOURNAL ARTICLE
Tobias Suske, Helena Sorger, Gabriele Manhart, Frank Ruge, Nicole Prutsch, Mark W Zimmerman, Thomas Eder, Diaaeldin I Abdallah, Barbara Maurer, Christina Wagner, Susann Schönefeldt, Katrin Spirk, Alexander Pichler, Tea Pemovska, Carmen Schweicker, Daniel Pölöske, Emina Hubanic, Dennis Jungherz, Tony Andreas Müller, Myint Myat Khine Aung, Anna Orlova, Ha Thi Thanh Pham, Kerstin Zimmel, Thomas Krausgruber, Christoph Bock, Mathias Müller, Maik Dahlhoff, Auke Boersma, Thomas Rülicke, Roman Fleck, Elvin Dominic de Araujo, Patrick Thomas Gunning, Tero Aittokallio, Satu Mustjoki, Takaomi Sanda, Sylvia Hartmann, Florian Grebien, Gregor Hoermann, Torsten Haferlach, Philipp Bernhard Staber, Heidi Anne Neubauer, Alfred Thomas Look, Marco Herling, Richard Moriggl
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive immature T cell cancer. Mutations in IL7R have been analyzed genetically, but downstream effector functions such as STAT5A and STAT5B hyperactivation are poorly understood. Here, we studied the most frequent and clinically challenging STAT5BN642H driver in T cell development and immature T cell cancer onset and compared it with STAT5A hyperactive variants in transgenic mice. Enhanced STAT5 activity caused disrupted T cell development and promoted an early T cell progenitor-ALL phenotype, with upregulation of genes involved in T cell receptor (TCR) signaling, even in absence of surface TCR...
April 15, 2024: Journal of Clinical Investigation
#2
JOURNAL ARTICLE
Xing-Yu Cao, Jian-Ping Zhang, Yue Lu, Yan-Li Zhao, De-Yan Liu, Min Xiong, Rui-Juan Sun, Zhi-Jie Wei, Jia-Rui Zhou, Xian Zhang, Jun-Fang Yang, Jingjing Li, Peihua Lu
CD7-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown promising initial complete remission (CR) rates in patients with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia and lymphoblastic lymphoma (T-ALL/LBL). To enhance the remission duration, consolidation with allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered. Our study delved into the outcomes of 34 patients with r/r T-ALL/LBL who underwent allo-HSCT after achieving CR with autologous CD7 CAR-T therapy...
April 13, 2024: British Journal of Haematology
#3
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
#4
Maria Suprunowicz, Katarzyna Marcinkiewicz, Elżbieta Leszczyńska, Anna Krętowska-Grunwald, Marcin Płonowski, Mariola Tałałaj, Łucja Dakowicz, Maryna Krawczuk-Rybak, Małgorzata Sawicka-Żukowska
Methemoglobinemia is a potentially life-threatening, rare condition in which the oxygen-carrying capacity of hemoglobin is diminished. We present the case of a 3-year-old boy treated for T-cell acute lymphoblastic leukemia (T-ALL) who developed methemoglobinemia (MetHb 57.1%) as a side effect of ifosfamide administration. Due to his critical condition, the patient was transferred to the intensive care unit (ICU). The therapy included methylene blue administration, an exchange transfusion, catecholamine infusion, and steroids...
March 28, 2024: International Journal of Molecular Sciences
#5
JOURNAL ARTICLE
Zhenyang Gu, Fei Li, Meng Li, Lu Wang, Ning Lu, Xiangshu Jin, Lili Wang, Chunji Gao, Liping Dou, Daihong Liu
BACKGROUND: Real-world data on outcomes of upfront allogeneic hematopoietic stem cell transplantation (allo-HCT) for adult T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) patients in first complete remission (CR1) is still lacking. METHODS: A single center retrospective study was conducted from 94 consecutive patients received their first allo-HCT between 2010 and 2021, which include 76 patients received upfront allo-HCT and 18 patients received allo-HCT in non-upfront settings...
April 12, 2024: Annals of Hematology
#6
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
#7
JOURNAL ARTICLE
Judith Hounjet, Linde Van Aerschot, Kim De Keersmaecker, Marc Vooijs, Kim R Kampen
Natural resistance-associated macrophage protein 2 (NRAMP 2; also known as DMT1 and encoded by SLC11A2) is mainly known for its iron transport activity. Recently, the DMT1 isoform lacking the iron-response element (nonIRE) was associated with aberrant NOTCH pathway activity. In this report, we investigated the function of DMT1 nonIRE in normal and malignant hematopoiesis. Knockdown of Dmt1 nonIRE in mice showed that it has non-canonical functions in hematopoietic stem cell differentiation: its knockdown suppressed development along the myeloid and lymphoid lineages, while promoting the production of platelets...
April 9, 2024: FEBS Letters
#8
JOURNAL ARTICLE
Nadia Abbassi, Aicha Bourrahouat, Eduardo Couchonnal Bedoya, Cécile Pagan, Meriem El Qabli, Sana Maidoumi, Abdelouahed Belmalih, Olivier Guillaud, Najib Kissani, Abdelhak Abkari, Imane Chahid, Mohammed Abdoh Rafai, Nezha Mouane, Yamna Kriouile, Saadia Aidi, Moustpha Hida, Mounia Lakhdar Idrissi, Mohammed Faouzi Belahsen, Mohammed El Abkari, Maria Rkain, Zahi Ismaili, Azeddine Sedki, Muriel Bost, Nisrine Aboussair, Alain Lachaux
BACKGROUND AND STUDY AIMS: In Morocco the prevalence of Wilson disease (WD) and the spectrum of mutations are not known. The aim of the present study was to estimate the prevalence of WD in Morocco, to evaluate the phenotype among a large cohort of WD patients, and to characterize ATP7B variants in a subgroup of WD patients. PATIENTS AND METHODS: We collected data from 226 patients admitted to five university hospital centers in Morocco between 2008 and 2020. The diagnosis was based on clinical manifestations, function tests and biochemical parameters...
April 6, 2024: Clinics and Research in Hepatology and Gastroenterology
#9
JOURNAL ARTICLE
Vivek Singh, Ranjana Singh, Rashmi Kushwaha
Efficient classification of T-acute lymphoblastic leukemia (T-ALL) involves considering various factors, such as age, white blood cell count, and chromosomal alterations. However, studying protein markers are crucial to improving T-ALL patients' diagnosis and treatment. A study analyzing the expression of proteomes was conducted to identify promising early-stage biomarkers for T-ALL patients METHODS: Label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze the blood proteins of both patients and healthy individuals to identify new biomarkers for T-ALL...
March 28, 2024: Hematology, Transfusion and Cell Therapy
#10
JOURNAL ARTICLE
R Pradeep, Sudeshna Rakshit, Geetha Shanmugam, Melvin George, Koustav Sarkar
BACKGROUND: T-ALL is an aggressive hematological tumor that develops as the result of a multi-step oncogenic process which causes expansion of hematopoietic progenitors that are primed for T cell development to undergo malignant transformation and growth. Even though first-line therapy has a significant response rate, 40% of adult patients and 20% of pediatric patients will relapse. Therefore, there is an unmet need for treatment for relapsed/refractory T-ALL to develop potential targeted therapies...
April 4, 2024: Clinical Immunology: the Official Journal of the Clinical Immunology Society
#11
JOURNAL ARTICLE
Lan Luo, Yang Jiao, Yan Li, Ping Yang, Jinjie Gao, Sai Huang, Wenyang Huang, Jijun Wang, Fei Dong, Xiaoyan Ke, Dehui Zou, Chunji Gao, Hongmei Jing
T lymphoblastic leukemia /lymphoma (T-ALL/LBL) is a rare and highly aggressive neoplasm of lymphoblasts. We evaluated 195 T-ALL/LBL adolescent and adult patients who received ALL-type chemotherapy alone (chemo,n = 72) or in combination with autologous hematopoietic stem cell transplantation(auto-HSCT,n = 23) or allogeneic hematopoietic stem cell transplantation(allo-HSCT,n = 100) from January 2006 to September 2020 in three Chinese medical centers. 167 (85.6%) patients achieved overall response (ORR) with 138 complete response (CR) patients (70...
April 6, 2024: Annals of Hematology
#12
JOURNAL ARTICLE
Yang Liu, Suqian Zhang, Yajuan Tan
Objective: To study whether and, if so, how honokiol overcome dexamethasone resistance in DEX-resistant CEM-C1 cells. Methods: We investigated the effect of honokiol (0-20 µM) on cell proliferation, cell cycle, cell apoptosis and autophagy in DEX-resistant CEM-C1 cells and DEX-sensitive CEM-C7 cells. We also determined the role of c-Myc protein and mRNA in the occurrence of T-ALL associated dexamethasone resistance western blot and reverse transcription-qPCR (RT-qPCR) analysis. Results: Cell Counting Kit (CCK)-8 assay shows that DEX-resistant CEM-C1 cell lines were highly resistant to dexamethasone with IC50 of 364...
December 2024: Hematology (Amsterdam, Netherlands)
#13
Shruti Shah, Rupayan Kundu, Rahul Mishra, Sudipto Mukherjee, Abhay Singh
T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is a rare and aggressive leukemia. Philadelphia chromosome-positive cytogenetic abnormality is most common in CML. It is difficult to differentiate between de novo Ph+ T-ALL/LBL and T-cell lymphoblastic crises of CML. We present a case of adult Ph+ T-ALL/LBL with a likely history of antecedent CML. Initially thought to be a case of chronic-phase CML, a diagnostic quandary led to the pursuit of a lymph node biopsy that established the diagnosis of Ph+ T-LBL or T lymphoblastic blast crisis of CML, a clinical presentation extremely rare and only the second of its kind from our review of the literature...
2024: Leukemia Research Reports
#14
JOURNAL ARTICLE
Xinyu Li, Shaofen Lin, Ning Liao, Huirong Mai, Xingjiang Long, Lili Liu, Beiyan Wu, Qiwen Chen, Qian Kong, Xianling Kong, Lixia Liu, Jiayue Qin, Jianpei Fang, Dunhua Zhou
The next-generation sequencing technologies application discovers novel genetic alterations frequently in pediatric acute lymphoblastic leukemia (ALL). RAS signaling pathway mutations at the time of relapse ALL frequently appear as small subclones at the time of onset, which are considered as the drivers in ALL relapse. Whether subclones alterations in the RAS signaling pathway should be considered for risk group stratification of ALL treatment is not decided yet. In this work, we investigate the RAS signaling pathway mutation spectrum and the related prognosis in pediatric ALL...
May 2024: Hematological Oncology
#15
JOURNAL ARTICLE
Sabina Enlund, Indranil Sinha, Christina Neofytou, Amanda Ramilo Amor, Konstantinos Papadakis, Anna Nilsson, Qingfei Jiang, Ola Hermanson, Frida Holm
A major obstacle in improving survival in pediatric T-cell acute lymphoblastic leukemia is understanding how to predict and treat leukemia relapse in the CNS. Leukemia cells are capable of infiltrating and residing within the CNS, primarily the leptomeninges, where they interact with the microenvironment and remain sheltered from systemic treatment. These cells can survive in the CNS, by hijacking the microenvironment and disrupting normal functions, thus promoting malignant transformation. While the protective effects of the bone marrow niche have been widely studied, the mechanisms behind leukemia infiltration into the CNS and the role of the CNS niche in leukemia cell survival remain unknown...
March 30, 2024: Experimental Cell Research
#16
JOURNAL ARTICLE
Zhenyu Zhang, Yu Jing, Bin Chen, Hong Zhang, Tuo Liu, Shuran Dong, Lei Zhang, Xiaoyan Yan, Shaobin Yang, Long Chen, Yani Lin, Kun Ru
INTRODUCTION: Acute lymphoblastic leukemia (ALL) is characterized by highly genetic heterogeneity, owing to recurrent fusion genes, gene mutations, intragenic deletion, and gene overexpression, which poses significant challenges in clinical detection. RNA sequencing (RNA-seq) is a powerful tool for detecting multiple genetic abnormalities, especially cryptic gene rearrangements, in a single test. METHODS: Sixty samples (B-ALL, n = 49; T-ALL, n = 9; mixed phenotype acute leukemia (MPAL), n = 2) and 20 controls were analyzed by targeted RNA-seq panel of 507 genes developed by our lab...
March 29, 2024: International Journal of Laboratory Hematology
#17
JOURNAL ARTICLE
Kevin W O'Connor, Kensei Kishimoto, Irena O Kuzma, Kelsey P Wagner, Jonathan S Selway, Justine E Roderick, Keshab K Karna, Kayleigh M Gallagher, Kai Hu, Haibo Liu, Rui Li, Michael A Brehm, Lihua Julie Zhu, David J Curtis, Cedric S Tremblay, Michelle A Kelliher
Relapse in T-cell acute lymphoblastic leukemia (T-ALL) may signify the persistence of leukemia-initiating cells (L-ICs). Ectopic TAL1/LMO expression defines the largest subset of T-ALL, but its role in leukemic transformation and its impact on relapse-driving L-ICs remain poorly understood. In TAL1/LMO mouse models, double negative-3 (DN3; CD4- CD8- CD25+ CD44- ) thymic progenitors harbored L-ICs. However, only a subset of DN3 leukemic cells exhibited L-IC activity, and studies linking L-ICs and chemotolerance are needed...
March 29, 2024: Leukemia
#18
JOURNAL ARTICLE
Stien De Coninck, Juliette Roels, Beatrice Lintermans, Sara T'Sas, Tom Taghon, David J Curtis, Tim Pieters, Steven Goossens, Pieter Van Vlierberghe
TET2-mediated DNA demethylation plays a pivotal role in regulating pre-leukemic clonal expansion in acute myeloid leukemia (AML), where TET2 mutations are also linked to AML progression. However, its function in other types of leukemias, including T-cell acute lymphoblastic leukemia (T-ALL), remains unclear. Here, we used two different T-ALL mouse models to study the possible tumor suppressor role of Tet2 in pre-leukemic T-ALL. Overexpression of Tet2 resulted in a mild but significant increase in T-ALL latency in the immature CD2-Lmo2tg T-ALL mouse model, but no effect on survival was observed in the mature Lck-Cretg/+ Ptenfl/lf T-ALL mouse model...
March 27, 2024: Blood Advances
#19
JOURNAL ARTICLE
Danyang Li, Yigang Yuan, Chen Meng, Zihan Lin, Min Zhao, Liuzhi Shi, Min Li, Daijiao Ye, Yue Cai, Xiaofei He, Haige Ye, Shujuan Zhou, Haixia Zhou, Shenmeng Gao
BACKGROUND: miR-182 promoter hypermethylation frequently occurs in various tumors, including acute myeloid leukemia, and leads to low expression of miR-182. However, whether adult acute lymphocyte leukemia (ALL) cells have high miR-182 promoter methylation has not been determined. METHODS: To assess the methylation status of the miR-182 promoter, methylation and unmethylation-specific PCR analysis, bisulfite-sequencing analysis, and MethylTarget™ assays were performed to measure the frequency of methylation at the miR-182 promoter...
March 26, 2024: Clinical Epigenetics
#20
JOURNAL ARTICLE
Giby V George, Maggie Kajstura, Andrew G Evans, Chauncey R Syposs
Gamma delta (γδ) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is a rare, aggressive subtype of T-lymphoid leukemia that accounts for only 9-12% of all T-ALL cases. Herein, we report the case of an 8-year-old boy who presented with facial swelling, shortness of breath, and progressive cervical and axillary lymphadenopathy. Pathological examination, flow cytometry (Navios, Beckman Coulter ClearLLab 10C 10-color T-cell panel [containing FITC-labeled TCR γδ antibody]), chromosomal analysis, interphase FISH, and targeted DNA-based NGS (34-gene Illumina TruSeq Myeloid Panel) were performed...
March 25, 2024: Journal of Hematopathology
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