A5029115176- Acute Lymphoblastic Leukemia research
- Acute Myeloid Leukemia Research
- Neuroblastoma Research and Treatments
- Hematopoietic Stem Cell Transplantation
- Sarcoma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Cancer therapeutics and mechanisms
- Lymphoma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Blood groups and transfusion
- Chronic Myeloid Leukemia Treatments
- Childhood Cancer Survivors' Quality of Life
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Chronic Lymphocytic Leukemia Research
- Parvovirus B19 Infection Studies
- Erythrocyte Function and Pathophysiology
- Hemoglobinopathies and Related Disorders
- Hematological disorders and diagnostics
- Renal and related cancers
- Lung Cancer Treatments and Mutations
- Protein Tyrosine Phosphatases
- Transplantation: Methods and Outcomes
- Virus-based gene therapy research
- Neuroendocrine Tumor Research Advances
Teikyo University
2023-2025
The University of Tokyo
2014-2024
Pediatrics and Genetics
2024
Kyoto University
2023
Stem Cell Institute
2023
Wellcome/MRC Cambridge Stem Cell Institute
2023
Teikyo University Hospital
2023
University of Tokyo Hospital
2012-2022
St. Jude Children's Research Hospital
2007-2012
Abstract Although hepatoblastoma is the most common pediatric liver cancer, its genetic heterogeneity and therapeutic targets are not well elucidated. Therefore, we conducted a multiomics analysis, including mutatome, DNA methylome, transcriptome analyses, of 59 samples. Based on methylation patterns, was classified into three clusters exhibiting remarkable correlation with clinical, histological, features. Cluster F largely composed cases fetal histology good outcomes, whereas E1 E2...
Abstract Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 ( CXCR4 ) gene. We characterize unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct genetic variants within our cohort, 11 were novel pathogenic affecting 15 individuals (23%). All affect same region impair...
KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) represents the most refractory type of childhood leukemia. To uncover molecular heterogeneity this disease, we perform RNA sequencing, methylation array analysis, whole exome and targeted deep sequencing on 84 infants with Our multi-omics clustering followed by single-sample single-cell inference hematopoietic differentiation establishes five robust integrative clusters (ICs) different master transcription factors, fusion partners...
Abstract PTPN11 has been identified as a causative gene in Noonan syndrome (NS), responsible for about 50% of cases NS. Given the association between NS and an increased risk some malignancies, notably leukemia probably solid tumors including neuroblastoma (NB) rhabdomyosarcoma (RMS), recent studies have reported that gain‐of‐function somatic mutations occur hematological especially de novo juvenile myelomonocytic (JMML) such NB, although at low frequency. In screen 7 cell lines 30 fresh RMS...
Abstract Novel therapeutic strategies are urgently required for osteosarcoma, given the early age at onset and persistently high mortality rate. Modern transcriptomics techniques can identify differentially expressed genes (DEGs) that may serve as biomarkers targets, so we screened DEGs in osteosarcoma. We found osteosarcoma cases could be divided into fair poor survival groups based on gene expression profiles. Among upregulated group, siRNA-mediated knockdown of glycosylation-related...
Abstract Leukemic stem cells exhibit several dysregulated pathways, with the Janus kinase (JAK) and signal transducer activator of transcription (STAT) pathway being among most prominent. Additionally, phosphorylated STAT3 is observed following prolonged activation anaplastic lymphoma (ALK) ligand-binding site, although level phospho-STAT3 induced by ligand-independent ALK exponentially higher. In ALK-positive tumors, ALK-STAT3 promotes tumor cell outgrowth directly prevents apoptosis. The...
To provide better insight into the genetic signatures of neuroblastomas, we analyzed 500 neuroblastomas (included specimens from JNBSG) using targeted-deep sequencing for 10 neuroblastoma-related genes and SNP arrays analysis. ALK expression was evaluated immunohistochemical analysis in 259 samples. Based on alterations, following 6 subgroups were identified: groups A (ALK abnormalities), B (other gene mutations), C (MYCN amplification), D (11q loss heterozygosity [LOH]), E (at least 1 copy...
Abstract Minimal residual disease (MRD) is usually defined as the small number of cancer cells that remain in body after treatment. The clinical significance MRD kinetics well recognized treatment hematologic malignancies, particularly acute lymphoblastic leukemia (ALL). Real time quantitative PCR targeting immunoglobulin (Ig) or T-cell receptor (TCR) rearrangement (PCR-MRD), multiparametric flow cytometric analysis antigen expression, are widely used detection. In this study, we devised an...
Abstract Neuroblastomas require novel therapies that are based on the exploitation of their biological mechanism. To address this need, we analyzed DNA methylation and expression datasets neuroblastomas, extracted a candidate gene characterizing aggressive features, conducted functional studies. Based data, identified subgroup neuroblastoma cases with 11q loss heterozygosity extremely poor prognosis. PHGDH , serine metabolism-related gene, was as strong characteristic in well MYCN...
NIPA (nuclear interaction partner of ALK) is an F-box-like protein that monitors the timing mitotic entry. Constitutively active delays entry by preventing accumulation nuclear cyclin B1. Here, we have investigated consequences Nipa inactivation using a conditional knockout strategy. Nipa-deficient animals are viable but show lower birth rate and reduced body weight. Furthermore, males sterile owing to block spermatogenesis during meiotic prophase. Whereas Nipa−/− mouse embryonic fibroblasts...
Abstract Aberrant micro-RNA (miRNA) expression profiles have been associated with disease progression and clinical outcome in pediatric cancers. However, few studies analyzed genome-wide dysregulation of miRNAs messenger RNAs (mRNAs) B-cell precursor acute lymphoblastic leukemia (BCP-ALL). To identify novel prognostic factors, we comprehensively investigated miRNA mRNA sequencing (miRNA-seq mRNA-seq) data BCP-ALL samples poor outcome. We 180 patients, including 43 matched pairs at diagnosis...
Abstract RAD51 is the only identified autosomal dominant gene to date causative of Fanconi anemia (FA) due negative effects. Only two patients with RAD51‐associated FA have been reported atypical phenotypes without bone marrow failure. We describe a new Asian patient novel mutation, presenting multiple congenital anomalies and chromosomal instability. The was 9‐year‐old Japanese girl. She had strabismus, myopia, submucous cleft palate, bilateral hearing impairment, scoliosis. also growth...
Abstract Malignant rhabdoid tumors (MRTs) are rare, highly aggressive embryonal neoplasms caused by biallelic alterations of the SMARCB1 gene. MRTs may occur in any soft tissue, but extracranial extrarenal extremely rare. Diagnosis unusual locations and with an uncharacteristic cytomorphology that mimics other is difficult. This was atypical case MRT a 15‐year‐old female closely resembled yolk sac tumors. It challenging to diagnose without confirming status.
Mutations in the MECOM encoding EVI1 are observed infants who have radioulnar synostosis with amegakaryocytic thrombocytopenia. MECOM-associated syndrome was proposed based on clinical heterogeneity. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for progressive bone marrow failure. However, data regarding allogeneic HSCT this rare disease limited. We retrospectively assessed overall survival, conditioning regimen, regimen-related toxicities and long-term...
We describe a neonate with abdominal distension, massive hepatomegaly, and high serum neuron-specific enolase level suggestive of congenital neuroblastoma. The patient died pulmonary hemorrhage after therapy. Autopsy revealed that the tumor cells in liver indicated acute megakaryocytic leukemia RBM15-MKL1 fusion gene.
Abstract To elucidate the molecular pathogenesis of pediatric germ cell tumors (GCTs), we performed DNA methylation array analysis, whole transcriptome sequencing, targeted capture and single-nucleotide polymorphism analysis using 51 GCT samples (25 female, 26 male), including 6 germinomas, 2 embryonal carcinomas, 4 immature teratomas, 3 mature 30 yolk sac tumors, mixed tumors. Among samples, 11 were from infants, 23 young children, 17 those aged ≥10 years. Sixteen developed in extragonadal...