Validation of the molecular international prognostic scoring system in patients with myelodysplastic syndromes defined by international consensus classification.

Myelodysplastic syndromes (MDS) have varied prognoses and require a risk-adapted treatment strategy for treatment optimization. Recently, a molecular prognostic model (Molecular International Prognostic Scoring System [IPSS-M]) that combines clinical parameters, cytogenetic abnormalities, and mutation topography was proposed. This study validated the IPSS-M in 649 patients with primary MDS (based on the 2022 International Consensus Classification [ICC]) and compared its prognostic power to those of the IPSS and revised IPSS (IPSS-R).

Validation of the prognostic significance of the 2022 European LeukemiaNet risk stratification system in intensive chemotherapy treated aged 18 to 65 years patients with de novo acute myeloid leukemia.

The European LeukemiaNet (ELN) recently proposed a revised recommendation for the diagnosis and management of acute myeloid leukemia (AML) in adults, recognized as ELN-2022. However, validation in a large real-world cohort remains lacking. In this study, we aimed to validate the prognostic relevance of the ELN-2022 in a cohort of 809 de novo, non-M3, younger (ages 18-65 years) AML patients receiving standard chemotherapy.

Poor prognostic implications of myelodysplasia-related mutations in both older and younger patients with de novo AML.

A set of myelodysplasia-related (MDS-R) gene mutations are incorporated into the 2022 European LeukemiaNet risk classification as adverse genetic factors for acute myeloid leukemia (AML) based on their poor prognostic impact on older patients. The impact of these mutations on younger patients (age < 60 years) remains elusive. In the study of 1213 patients with de novo non-M3 AML, we identified MDS-R mutations in 32.

Clinico-genetic and prognostic analyses of 716 patients with primary myelodysplastic syndrome and myelodysplastic syndrome/acute myeloid leukemia based on the 2022 International Consensus Classification.

The 2022 International Consensus Classification (ICC) recategorized myeloid neoplasms based on recent advances in the understanding of the biology of hematologic malignancies, in which myelodysplastic syndrome (MDS) with blasts of 10%-19% is classified as MDS/acute myeloid leukemia (AML), MDS with mutated SF3B1, irrespective of the number of ring sideroblasts, as MDS-SF3B1, and those with multi-hit TP53 mutations as MDS with mutated TP53. In the analysis of 716 patients with MDS diagnosed according to the 2016 WHO classification, we found that 75.3% of patients remained in the MDS group based on the ICC, while 24.

Distinct genetic landscapes and their clinical implications in younger and older patients with myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a group of clinically and genetically diverse diseases that impose patients with an increased risk of leukemic transformation. While MDS is a disease of the elderly, the interplay between aging and molecular profiles is not fully understood, especially in the Asian population. Thus, we compared the genetic landscape between younger and older patients in a cohort of 698 patients with primary MDS to advance our understanding of the distinct pathogenesis and different survival impacts of gene mutations in MDS according to age.

Effect of mutation allele frequency on the risk stratification of myelodysplastic syndrome patients.

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal myeloid malignancies. Though several recurrent mutations are closely correlated with clinical outcomes, data concerning the association between mutation variant allele frequencies (VAF) and prognosis are limited. In this study, we performed comprehensive VAF analyses of relevant myeloid-malignancy related mutations in 698 MDS patients and correlated the results with their prognosis.

Distinct clinico-biological features in AML patients with low allelic ratio FLT3-ITD: role of allogeneic stem cell transplantation in first remission.

The mutant burden of FLT3-ITD modulates its prognostic impact on patients with acute myeloid leukemia (AML). However, for patients with low allelic ratio (AR) FLT3-ITD (FLT3-ITD, AR < 0.5), clinical features, as well as genomic and transcriptomic profiles remain unclear, and evidence supporting allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) remains controversial.

Clinical implications of sequential MRD monitoring by NGS at 2 time points after chemotherapy in patients with AML.

Next-generation sequencing (NGS) has been applied to measurable/minimal residual disease (MRD) monitoring after induction chemotherapy in patients with acute myeloid leukemia (AML), but the optimal time point for the test remains unclear. In this study, we aimed to investigate the clinical significance of NGS MRD at 2 different time points. We performed targeted NGS of 54 genes in bone marrow cells serially obtained at diagnosis, first complete remission (first time point), and after the first consolidation chemotherapy (second time point) from 335 de novo AML patients.

Compact optical diagnostic device for isothermal nucleic acids amplification.

We recently reported the successful use of the loop-mediated isothermal amplification (LAMP) reaction for hepatitis B virus (HBV) DNA amplification and its optimal primer design method. In this study, we report the development of an integrated isothermal device for both amplification and detection of targeted HBV DNA. It has two major components, a disposable polymethyl methacrylate (PMMA) micro-reactor and a temperature-regulated optical detection unit (base apparatus) for real-time monitoring of the turbidity changes due to the precipitation of DNA amplification by-product, magnesium pyrophosphate.

Nick-directed repair of palindromic loop mismatches in human cell extracts.

Palindromic sequences present in DNA may form secondary structures that block DNA replication and transcription causing adverse effects on genome stability. It has been suggested that hairpin structures containing mispaired bases could stimulate the repair systems in human cells. In this study, processing of variable length of palindromic loops in the presence or absence of single-base mismatches was investigated in human cell extracts.

DNA loop repair by Escherichia coli cell extracts.

The nick-directed DNA repair efficiency of a set of M13mp18-derived heteroduplexes containing 8-, 12-, 16-, 22-, 27-, 45-, and 429-nucleotide loops was determined by in vitro assay. Unpaired nucleotides of each heteroduplex reside within overlapping recognition sites for two restriction endonucleases, permitting independent evaluation of repair occurring on either DNA strand. Our results show that a strand break located either 3' or 5' to the loop is sufficient to direct heterology repair to the nicked strand in Escherichia coli extracts.