Serial monitoring of circulating tumour DNA on clinical outcome in myelodysplastic syndromes and acute myeloid leukaemia.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhou X
PROVIDER: S-EPMC10368807 | biostudies-literature | 2023 Jul
REPOSITORIES: biostudies-literature
Publications
Serial monitoring of circulating tumour DNA on clinical outcome in myelodysplastic syndromes and acute myeloid leukaemia.
Zhou Xinping X Lang Wei W Mei Chen C Ren Yanling Y Ma Liya L Jiang Lingxu L Ye Li L Xu Gaixiang G Luo Yingwan Y Liu Lixia L Cao Shanbo S Qin Jiayue J Tong Hongyan H
Clinical and translational medicine 20230701 7
Similar Datasets
Project description:A 10K cDNA microarray was used to compare neutrophil RNA from 21 MDS patient and 2 AML patients to pooled neutrophil RNA from 7 healthy controls.
2005-01-09 | E-GEOD-971 | biostudies-arrayexpress
Project description:A 10K cDNA microarray was used to compare neutrophil RNA from 21 MDS patient and 2 AML patients to pooled neutrophil RNA from 7 healthy controls. Keywords: repeat sample
2005-01-10 | GSE971 | GEO
Project description:The implementation of next-generation sequencing (NGS) has influenced diagnostic, prognostic, and therapeutic decisions in myeloid malignancies. However, the clinical relevance of serial molecular annotation in patients with myelodysplastic syndrome (MDS) undergoing active treatment is unknown. MDS or secondary acute myeloid leukemia (sAML) patients who had at least two NGS assessments were identified. Outcomes according to mutation clearance (NGS-) on serial assessment were investigated. Univariate and multivariate Cox regression models were used to evaluate the prognostic impact of NGS trajectory on overall survival (OS). A total of 157 patients (MDS [n = 95]; sAML [n = 52]; CMML [n = 10]) were identified, with 93% of patients receiving treatment between NGS assessments. Magnitude of VAF delta from baseline was significantly associated with quality of response to treatment. Patients achieving NGS- had significantly improved OS compared to patients with mutation persistence (median OS not reached vs. 18.5 months; P = 0.002), which was confirmed in multivariate analysis (HR,0.14; 95%CI = 0.03-0.56; P = 0.0064). Serial TP53 VAF evaluation predicts outcomes with TP53 clearance representing an independent covariate for superior OS (HR,0.22; 95%CI = 0.05-0.99; P = 0.048). Collectively, our study highlights the clinical value of serial NGS during treatment and warrants prospective validation of NGS negativity as a biomarker for treatment outcome.
| S-EPMC7854836 | biostudies-literature
Project description:TP53 mutations are less frequent in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) than in solid tumors, except in secondary and therapy-related MDS/AMLs, and in cases with complex monosomal karyotype. As in solid tumors, missense mutations predominate, with the same hotspot mutated codons (particularly codons 175, 248, 273). As TP53-mutated MDS/AMLs are generally associated with complex chromosomal abnormalities, it is not always clear when TP53 mutations occur in the pathophysiological process. It is also uncertain in these MDS/AML cases, which often have inactivation of both TP53 alleles, if the missense mutation is only deleterious through the absence of a functional p53 protein, or through a potential dominant-negative effect, or finally a gain-of-function effect of mutant p53, as demonstrated in some solid tumors. Understanding when TP53 mutations occur in the disease course and how they are deleterious would help to design new treatments for those patients who generally show poor response to all therapeutic approaches.
| S-EPMC10136154 | biostudies-literature
Project description:Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies arising from the bone marrow. Despite recent advances in treating these diseases, patients with higher-risk MDS and AML continue to have a poor prognosis with limited survival. It has long been recognized that there is an immune component to the pathogenesis of MDS and AML, but until recently, immune therapies have played a limited role in treating these diseases. Immune suppressive therapy exhibits durable clinical responses in selected patients with MDS, but the question of which patients are most suitable for this treatment remains unclear. Over the past decade, there has been remarkable progress in identifying genomic features of MDS and AML, which has led to an improved discernment of the molecular pathogenesis of these diseases. An improved understanding of immune and inflammatory molecular mechanisms of MDS and AML have also recently revealed novel therapeutic targets. Emerging treatments for MDS and AML include monoclonal antibodies such as immune checkpoint inhibitors, bispecific T-cell-engaging antibodies, antibody drug conjugates, vaccine therapies, and cellular therapeutics including chimeric antigen receptor T-cells and NK cells. In this review, we provide an overview of the current understanding of immune dysregulation in MDS and AML and an update on novel immune therapies for these bone marrow malignancies.
| S-EPMC8507987 | biostudies-literature
Project description:Epigenetic mechanisms affecting chromatin structure contribute to regulate gene expression and assure the inheritance of information, which are essential for the proper expression of key regulatory genes in healthy cells, tissues and organs. In the medical field, an increasing body of evidence indicates that altered gene expression or de-regulated gene function lead to disease. Cancer cells also suffer a profound change in the genomic methylation patterns and chromatin status. Aberrant DNA methylation patterns, changes in chromatin structure and in gene expression are common in all kind of tumor types. However, studies on leukemias have provided paradigmatic examples for the functional implications of the epigenetic alterations in cancer development and progression as well as their relevance for therapeutical targeting.
| S-EPMC2764862 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of many solid tumors, with limited progress made in the area of myeloid malignancies. The low mutational burden of acute myeloid leukemia (AML) is one potential reason behind the lack of activity of T-cell harnessing ICIs, particularly CTLA-4 and PD-1 inhibitors. Innate immune checkpoints play a critical role in the immune escape of AML and myelodysplastic syndromes (MDS). The CD47 targeting agent, magrolimab, has shown promising activity when combined with azacitidine in early phase trials conducted in AML and higher-risk MDS, especially among patients harboring a TP53 mutation. Similarly, sabatolimab (an anti-TIM-3 monoclonal antibody) plus hypomethylating agents have shown durable responses in higher-risk MDS and AML in early clinical trials. Randomized trials are currently ongoing to confirm the efficacy of these agents. In this review, we will present the current progress and future directions of immune checkpoint inhibition in AML and MDS.
| S-EPMC9318025 | biostudies-literature
Project description:BackgroundThe molecular determinants of clinical responses to decitabine therapy in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) are unclear.MethodsWe enrolled 84 adult patients with AML or MDS in a single-institution trial of decitabine to identify somatic mutations and their relationships to clinical responses. Decitabine was administered at a dose of 20 mg per square meter of body-surface area per day for 10 consecutive days in monthly cycles. We performed enhanced exome or gene-panel sequencing in 67 of these patients and serial sequencing at multiple time points to evaluate patterns of mutation clearance in 54 patients. An extension cohort included 32 additional patients who received decitabine in different protocols.ResultsOf the 116 patients, 53 (46%) had bone marrow blast clearance (<5% blasts). Response rates were higher among patients with an unfavorable-risk cytogenetic profile than among patients with an intermediate-risk or favorable-risk cytogenetic profile (29 of 43 patients [67%] vs. 24 of 71 patients [34%], P<0.001) and among patients with TP53 mutations than among patients with wild-type TP53 (21 of 21 [100%] vs. 32 of 78 [41%], P<0.001). Previous studies have consistently shown that patients with an unfavorable-risk cytogenetic profile and TP53 mutations who receive conventional chemotherapy have poor outcomes. However, in this study of 10-day courses of decitabine, neither of these risk factors was associated with a lower rate of overall survival than the rate of survival among study patients with intermediate-risk cytogenetic profiles.ConclusionsPatients with AML and MDS who had cytogenetic abnormalities associated with unfavorable risk, TP53 mutations, or both had favorable clinical responses and robust (but incomplete) mutation clearance after receiving serial 10-day courses of decitabine. Although these responses were not durable, they resulted in rates of overall survival that were similar to those among patients with AML who had an intermediate-risk cytogenetic profile and who also received serial 10-day courses of decitabine. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT01687400 .).
| S-EPMC5217532 | biostudies-literature
Project description:Although most cases of myeloid neoplasms are sporadic, a small subset has been associated with germline mutations. The 2016 revision of the World Health Organization classification included these cases in a myeloid neoplasm group with a predisposing germline mutational background. These patients must have a different management and their families should get genetic counseling. Cases identification and outline of the major known syndromes characteristics will be discussed in this text.
| S-EPMC5600909 | biostudies-literature
Project description: Not available
| S-EPMC5394857 | biostudies-literature