This study aimed to assess the prognostic influences of Wilms tumor 1 (WT1) gene mutations in cytogenetically normal acute myeloid leukemia (CN-AML) among Egyptian patients. Exon 7 of WT1 was screened for mutations in samples from 82 CN-AML patients out of 203 newly diagnosed AML patients, using a high-resolution capillary electrophoresis. Seven out of 82 AML patients (8.3 %) harbored WT1 mutations. There was no significant difference between the mutant WT1 and wild type AML patients as regard age, sex, French-American-British subtypes and the prevalence of success of induction remission therapy (P < 0.5). AML patients with mutant WT1 had shorter overall survival as compared to those patients with wild WT1 (HR = 1.38; 95 % CI 4.79-6.86; P = 0.004). In conclusion, CN-AML patients with WT1 gene mutation have poor clinical outcome. We recommend testing the WT1 mutations as part of molecularly based risk assessment and risk-adapted treatment stratification of patients with CN-AML.
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http://dx.doi.org/10.1007/s12288-013-0288-6 | DOI Listing |
BMJ Oncol
July 2024
Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Objective: Acute myeloid leukaemia (AML) prognosis is enhanced with intensive remission induction chemotherapy (ICT) in eligible patients. However, ICT eligibility perceptions may differ among healthcare professionals. This nationwide, population-based study aimed to explore regional variation in ICT application and its relation with overall survival (OS).
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School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar - Delhi, Punjab, India.
Introduction: Acute Myeloid Leukemia is a heterogeneous hematological malignancy characterized by the uncontrolled proliferation of abnormal myeloid cells. Besides several other genetic abnormalities developed in AML, FLT3 mutations are significant due to their worse prognostic impacts and therapeutic resistance. As a result, these mutations enable AML cells to develop mechanisms for evading immune surveillance.
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January 2025
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, 8174673461, Iran.
Acute myeloid leukemia (AML) is caused by altered maturation and differentiation of myeloid blasts, as well as transcriptional/epigenetic alterations, all leading to excessive proliferation of malignant blood cells in the bone marrow. Tumor heterogeneity due to the acquisition of new somatic alterations leads to a high rate of resistance to current therapies or reduces the efficacy of hematopoietic stem cell transplantation (HSCT), thus increasing the risk of relapse and mortality. Single-cell RNA sequencing (scRNA-seq) will enable the classification of AML and guide treatment approaches by profiling patients with different facets of the same disease, stratifying risk, and identifying new potential therapeutic targets at the time of diagnosis or after treatment.
View Article and Find Full Text PDFActa Pharmacol Sin
January 2025
School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
FMS-like tyrosine kinase-3 (FLT3), a class 3 receptor tyrosine kinase, can be activated by mutations of internal tandem duplication (FLT3-ITD) or point mutations in the tyrosine kinase domain (FLT3-TKD), leading to constitutive activation of downstream signaling cascades, including the JAK/STAT5, PI3K/AKT/mTOR and RAS/MAPK pathways, which promote the progression of leukemic cells. Despite the initial promise of FLT3 inhibitors, the discouraging outcomes in the treatment of FLT3-ITD-positive acute myeloid leukemia (AML) promote the pursuit of more potent and enduring therapeutic approaches. The histone acetyltransferase complex comprising the E1A binding protein P300 and its paralog CREB-binding protein (p300/CBP) is a promising therapeutic target, but the development of effective p300/CBP inhibitors faces challenges due to inherent resistance and low efficacy, often exacerbated by the absence of reliable clinical biomarkers for patient stratification.
View Article and Find Full Text PDFCogn Affect Behav Neurosci
January 2025
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Neurosciences | CCM, Berlin, Germany.
Anhedonia, i.e., the loss of pleasure or lack of reactivity to reward, is a core symptom of major psychiatric conditions.
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