A5031402779- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- Protein Degradation and Inhibitors
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Histone Deacetylase Inhibitors Research
- Hematopoietic Stem Cell Transplantation
- CNS Lymphoma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Lymphoma Diagnosis and Treatment
- Chronic Myeloid Leukemia Treatments
- Cancer, Hypoxia, and Metabolism
- Glioma Diagnosis and Treatment
- Blood disorders and treatments
- Hematological disorders and diagnostics
- Chronic Lymphocytic Leukemia Research
- Hemoglobinopathies and Related Disorders
- Sarcoma Diagnosis and Treatment
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Neutropenia and Cancer Infections
- Neuroblastoma Research and Treatments
- Neonatal Respiratory Health Research
- Nuclear Receptors and Signaling
- Immune Cell Function and Interaction
Yokohama City University
2017-2025
Yokohama City University Hospital
2017-2025
Gunma Children's Medical Center
2011-2019
National Hospital Organization
2017-2019
Nagoya Medical Center
2017-2019
Pediatrics and Genetics
2018
Gunma University
2007-2017
The University of Tokyo
2012-2013
Recent advances in high-throughput sequencing technologies have enabled a comprehensive dissection of the cancer genome clarifying large number somatic mutations wide variety types. A methods been proposed for mutation calling based on amount data, which is accomplished most cases by statistically evaluating difference observed allele frequencies possible single nucleotide variants between tumours and paired normal samples. However, an accurate detection remains challenge under low depths or...
Summary For successful chimeric antigen receptor T (CAR‐T) cell therapy, CAR‐T cells must be manufactured without failure caused by suboptimal expansion. In order to determine risk factors for manufacturing failure, we performed a nationwide cohort study in Japan and analysed patients with diffuse large B‐cell lymphoma (DLBCL) who underwent tisagenlecleucel production. We compared clinical between 30 cases that failed (7.4%) those succeeded ( n = 378). Among the failures, proportion of...
Abstract Innovations in sequencing technology have led to the discovery of novel mutations that cause inherited diseases. However, many patients with suspected genetic diseases remain undiagnosed. Long-read technologies are expected significantly improve diagnostic rate by overcoming limitations short-read sequencing. In addition, Oxford Nanopore Technologies (ONT) offers adaptive sampling and computationally driven target enrichment technology. This enables more affordable intensive...
The cryptic t(5;11)(q35;p15.5) creates a fusion gene between the NUP98 and NSD1 genes. To ascertain significance of this fusion, we explored its frequency, clinical impact, expression pattern using DNA microarray in pediatric acute myeloid leukemia (AML) patients. NUP98‐NSD1 transcripts were detected 6 (4.8%) 124 AML Supervised hierarchical clustering analyses probe sets that differentially expressed these patients characteristic pattern, including 18 ‐negative ( ‐like patients). In total,...
Key Points Using RNA-seq in pediatric AML patients, 5 gene rearrangements were newly identified, including NPM1 and RUNX1 rearrangements. unmasked the complexity of alterations by identifying disease-causing nearly all patients.
Acute myeloid leukaemia (AML) is a molecularly and clinically heterogeneous disease. Targeted sequencing efforts have identified several mutations with diagnostic prognostic values in KIT, NPM1, CEBPA FLT3 both adult paediatric AML. In addition, massively parallel enabled the discovery of recurrent (i.e. IDH1/2 DNMT3A) this study, whole-exome (WES) 22 AML patients revealed components cohesin complex (RAD21 SMC3), BCORL1 ASXL2 addition to previously known gene mutations. We also intratumoural...
Abstract Pediatric acute megakaryoblastic leukemia in non‐Down syndrome (AMKL) is a unique subtype of myeloid (AML). Novel CBFA2T3‐GLIS2 and NUP98‐KDM5A fusions recurrently found AMKL were recently reported as poor prognostic factors. However, their detailed clinical molecular characteristics patients treated with recent improved therapies remain uncertain. We analyzed features 44 on two Japanese AML protocols, the AML99 AML‐05 trials. identified , RBM15‐MKL1 KMT2A rearrangements 12 (27%), 4...
Summary Recent reports described the NUP 98‐ NSD 1 fusion as an adverse prognostic marker for acute myeloid leukaemia ( AML ) and PRDM 16 (also known MEL representative overexpressed gene in patients harbouring fusion. expression levels were measured via real‐time polymerase chain reaction 369 paediatric with de novo , of whom 84 (23%) exhibited overexpression / ABL ratio ≥ 0·010). The frequencies high or low differed widely respect to each genetic alteration, follows: t(8;21), 4% vs. 96%, P...
Abstract We investigated genome-wide DNA methylation patterns in 64 pediatric patients with acute myeloid leukemia (AML). Based on unsupervised clustering the 567 most variably methylated cytosine guanine dinucleotide (CpG) sites, were categorized into 4 clusters associated genetic alterations. Clusters 1 and 3 characterized by presence of known favorable prognostic factors, such as RUNX1-RUNX1T1 fusion KMT2A rearrangement low MECOM expression, biallelic CEBPA mutations (all 8 patients),...
Primary central nervous system lymphoma (PCNSL) is an isolated type of the and has a dismal prognosis despite intensive chemotherapy. Recent genomic analyses have identified highly recurrent mutations MYD88 CD79B in immunocompetent PCNSL, whereas LMP1 activation commonly observed Epstein-Barr virus (EBV)-positive PCNSL. However, lack clinically representative preclinical models hampered our understanding pathogenic mechanisms by which genetic aberrations drive PCNSL disease phenotypes. Here,...
Abstract High PRDM16 (also known as MEL1 ) expression is a representative marker of acute myeloid leukemia (AML) with NUP98‐NSD1 and significant predictive for poor prognosis in pediatric AML. However, the clinical features adult AML remain unclear. highly homologous to MDS1/EVI1 , which an alternatively spliced transcript MECOM EVI1 ). We investigated 151 patients, 47 (31%) exhibiting high ( PRDM16/ABL1 ratio ≥ 0.010). significantly correlated DNMT3A (43% vs. 15%, P < 0.001) NPM1 21%, =...
<title>Abstract</title> The RNA-sequencing data from the Japanese Children’s Cancer Group (JCCG)’s AML-05 study was re-analyzed to clarify mechanisms related high <italic>PRDM16</italic> expressions, which is independently associated with adverse outcomes. Results showed that 19 of 139 patients presented out-of-frame <italic>PRDM16::SKI</italic> fusions. Thus, gene expression levels in 369 and 329 AML-12 studies, respectively, were measured. In total, 119 (32%) 58 (18%) an aberrant...
Although infants (age <1 year) with acute myeloid leukaemia (AML) have unique characteristics and are vulnerable to chemotherapy, children aged 1-2 years AML may similar that of infants. Thus, we analysed 723 paediatric patients treated on the Japanese AML99 AML-05 trials identify younger children. We identified <3 (the group) as a distinct subgroup. KMT2A-rearrangement (KMT2A-R), CBFA2T3-GLIS2, CBFB-MYH11 NUP98-KDM5A were frequently found in group. Prognostic analyses revealed poor 5-year...
The prognosis of pediatric acute myeloid leukemia (AML) has improved via stratification therapy. However, relapse or death occurs in 30%-40% cases. Novel genetic factors for AML need to be elucidated improve prognosis. We detected recurrent internal tandem duplication upstream binding transcription factor (UBTF-ITD) 1.2% (6/503) Japanese patients with de novo AML. No UBTF-ITD was 175 adult 65 cell lines that included 15 AML, 39 lymphoblastic leukemia, five chronic and six neuroblastoma...
Abstract Risk classification in pediatric acute myeloid leukemia (P-AML) is crucial for personalizing treatments. Thus, we aimed to establish a risk-stratification tool P-AML patients and eventually guide individual treatment. A total of 256 with accredited mRNA-seq data from the TARGET database were divided into training internal validation datasets. gene-expression-based prognostic score was constructed overall survival (OS), by using univariate Cox analysis, LASSO regression Kaplan–Meier...
RAS pathway alterations have been implicated in the pathogenesis of various hematological malignancies. However, their clinical relevance pediatric acute myeloid leukemia (AML) is not well characterized. We analyzed frequency, significance, and prognostic 328 patients with de novo AML. were detected 80 (24.4%) patients: NF1 (n=7, 2.1%), PTPN11 (n=15, 4.6%), CBL (n=6, 1.8%), NRAS (n=44, 13.4%), KRAS (n=12, 3.7%). Most these mutually exclusive also together other aberrations signal...