Publications by authors named "Daichi Inoue"

This retrospective study aimed to clarify the cumulative live-birth rates (CLBRs) and cost per live-birth (LB) to evaluate the validity of frozen-thawed embryo transfer without preimplantation genetic testing for aneuploidy (PGT-A) in women aged ≥ 40 years. The study included 1,011 patients aged ≥ 40 years who underwent their first oocyte retrieval at our hospital between January 2010 and September 2017. They were followed up for up to two years or until either treatment discontinuation or a pregnancy that resulted in a live birth.

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Purpose: Controlled ovarian stimulation (COS) is vital for IVF. We have developed an AI system to support the implementation of COS protocols in our clinical group.

Methods: We developed two models as AI algorithms of the AI system.

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Structural variations involving enhancer hijacking induce aberrant oncogene expression and cause tumorigenesis. A rare translocation, t(3;8)(q26.2;q24), is associated with MECOM and MYC rearrangement, causing myeloid neoplasms with a dismal prognosis.

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Photochemical multi-component coupling reactions initiated by the activation of glycosyl bromides in the presence of 1,4-bis(diphenylamino)benzene (BDB) as an organic photocatalyst were developed. -glycosides accompanied by olefin (di)functionalization were obtained. This method allows us to access various -glycosides with alkene, carbonyl, alcohol, ether, and amide functionalities.

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To the best of our knowledge, this is the first case of pregnancy with a healthy baby after treatment with an oral gonadotropin-releasing hormone (GnRH) antagonist in women with premature ovarian insufficiency. A 36-year-old female presented at our hospital after being diagnosed with premature ovarian insufficiency by a previous doctor. We administered clomiphene, human menopausal gonadotropin (hMG), and GnRH antagonist (injection) together with estrogen replacement for 11 cycles (27 months), but no follicular development was observed.

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In the intricate orchestration of the central dogma, pre-mRNA splicing plays a crucial role in the post-transcriptional process that transforms DNA into mature mRNA. Widely acknowledged as a pivotal RNA processing step, it significantly influences gene expression and alters the functionality of gene product proteins. Although U2-dependent spliceosomes efficiently manage the removal of over 99% of introns, a distinct subset of essential genes undergo splicing with a different intron type, denoted as minor introns, using U12-dependent spliceosomes.

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Article Synopsis
  • ATP-dependent chromatin remodeling complexes, specifically non-canonical BAF (ncBAF), play important roles in hematopoietic stem cells (HSCs), but their functions haven't been fully explored.* -
  • The study focuses on BRD9, a key component of ncBAF, finding that its loss increases chromatin accessibility, leading to a preference for myeloid cell development while hindering B cell formation.* -
  • BRD9 is shown to interact with CTCF, which affects gene expression and chromatin structure in HSCs, highlighting ncBAF's crucial role in determining cell fate in both normal and cancerous blood cell development.*
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Purpose: To analyze whether response to the GnRH test is a predictor of empty follicle syndrome (EFS) and to analyze independent risk factors for EFS.

Methods: The GnRH test results of 3765 patients from 2016 to 2018 were used to define the reference range of the GnRH test. Risk factors for EFS were estimated by multivariate logistic analysis of 5282 cycles (5247 oocyte-retrieved cycles with GnRH agonist trigger and 35 cycles of EFS) conducted from 2016 to 2019.

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Despite recent advances in the treatment of acute myeloid leukemia (AML), there has been limited success in targeting surface antigens in AML, in part due to shared expression across malignant and normal cells. Here, high-density immunophenotyping of AML coupled with proteogenomics identified unique expression of a variety of antigens, including the RNA helicase U5 snRNP200, on the surface of AML cells but not on normal hematopoietic precursors and skewed Fc receptor distribution in the AML immune microenvironment. Cell membrane localization of U5 snRNP200 was linked to surface expression of the Fcγ receptor IIIA (FcγIIIA, also known as CD32A) and correlated with expression of interferon-regulated immune response genes.

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The process of RNA splicing plays a pivotal role in gene expression and genetic information modification by converting pre-mRNA into mature mRNA. Dysregulation of this process has been associated with aberrant gene expression and function, leading to hematopoietic malignancies. Through recent clinical and mouse model analyses, insights have been gained into the mechanisms underlying splicing factor mutations that aid in myelodysplastic syndrome and acute myeloid leukemia.

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SETBP1 is a potential epigenetic regulator whose hotspot mutations preventing proteasomal degradation are recurrently detected in myeloid malignancies with poor prognosis. It is believed that the mutant SETBP1 exerts amplified effects of wild-type SETBP1 rather than neomorphic functions. This indicates that dysregulated quantitative control of SETBP1 would result in the transformation of hematopoietic cells.

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Hematopoiesis is maintained and regulated by a bone marrow-specific microenvironment called a niche. In hematological malignancies, tumor cells induce niche remodeling, and the reconstructed niche is closely linked to disease pathogenesis. Recent studies have suggested that extracellular vesicles (EVs) secreted from tumor cells play a principal role in niche remodeling in hematological malignancies.

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Acquired sideroblastic anemia, characterized by bone marrow ring sideroblasts (RS), is predominantly associated with myelodysplastic syndrome (MDS). Although somatic mutations in splicing factor 3b subunit 1 (SF3B1), which is involved in the RNA splicing machinery, are frequently found in MDS-RS, the detailed mechanism contributing to RS formation is unknown. To explore the mechanism, we established human umbilical cord blood-derived erythroid progenitor-2 (HUDEP-2) cells stably expressing SF3B1.

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Unlabelled: Recently, screens for mediators of resistance to FLT3 and ABL kinase inhibitors in leukemia resulted in the discovery of LZTR1 as an adapter of a Cullin-3 RING E3 ubiquitin ligase complex responsible for the degradation of RAS GTPases. In parallel, dysregulated LZTR1 expression via aberrant splicing and mutations was identified in clonal hematopoietic conditions. Here we identify that loss of LZTR1, or leukemia-associated mutants in the LZTR1 substrate and RAS GTPase RIT1 that escape degradation, drives hematopoietic stem cell (HSC) expansion and leukemia in vivo.

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Pre-mRNA splicing is now widely recognized as a cotranscriptional and post-transcriptional mechanism essential for regulating gene expression and modifying gene product function. Mutations in genes encoding core spliceosomal proteins and accessory regulatory splicing factors are now considered among the most recurrent genetic abnormalities in patients with cancer, particularly hematologic malignancies. These include mutations in the major (U2-type) and minor (U12-type) spliceosomes, which remove >99% and ~0.

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Article Synopsis
  • Detailed analysis shows that genetic rearrangements of chromosome 3 drive certain myeloid leukemias by increasing EVI1 transcription through enhancer changes.
  • A novel EVI1 RNA variant, created by mutations in the splicing factor SF3B1, contributes to acute myeloid leukemia transformation and is frequently found in these patients.
  • Mutant SF3B1 promotes abnormal EVI1 splicing, enhancing stem cell self-renewal and accelerating leukemia development in mouse models, highlighting a crucial link between splicing mutations and myeloid leukemia pathogenesis.
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Article Synopsis
  • * MDS cells inhibit the normal functioning of mesenchymal stem cells (MSCs), crucial for supporting blood stem cells, by interfering with their development and bone metabolism.
  • * The study reveals that MDS cells release extracellular vesicles that contribute to this suppression, but this effect can be reversed by promoting MSC differentiation, suggesting potential pathways for treatment.
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The BCL2-inhibitor, Venetoclax (VEN), has shown significant anti-leukemic efficacy in combination with the DNMT-inhibitor, Azacytidine (AZA). To explore the mechanisms underlying the selective sensitivity of mutant leukemia cells to VEN and AZA, we used cell-based isogenic models containing a common leukemia-associated mutation in the epigenetic regulator ASXL1. KBM5 cells with CRISPR/Cas9-mediated correction of the ASXL1 mutation showed reduced leukemic growth, increased myeloid differentiation, and decreased HOXA and BCL2 gene expression in vitro compared to uncorrected KBM5 cells.

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Myelodysplastic syndrome (MDS) is a group of hematopoietic disorders with limited treatment options. Anemia is a common symptom in MDS, and although erythropoiesis-stimulating agents such as erythropoietin, lenalidomide, and luspatercept are available to treat anemia, many MDS patients do not respond to these first-line therapies. Therefore, alternative drug development strategies are needed to improve therapeutic efficacy.

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Article Synopsis
  • Eukaryotes use two pre-mRNA splicing systems: the major spliceosome for most introns and the minor spliceosome for rare introns, but the role of the minor spliceosome is not well understood.
  • Research shows that losing the minor spliceosome component ZRSR2 can boost the self-renewal of hematopoietic stem cells, indicating its regulatory importance.
  • Mutations in minor introns are linked to various cancers and disorders, such as Noonan syndrome, suggesting that minor intron recognition plays a critical role in blood cell development and cancer progression.
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Somatic mutations of ASXL1 are frequently detected in age-related clonal hematopoiesis (CH). However, how ASXL1 mutations drive CH remains elusive. Using knockin (KI) mice expressing a C-terminally truncated form of ASXL1-mutant (ASXL1-MT), we examined the influence of ASXL1-MT on physiological aging in hematopoietic stem cells (HSCs).

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In the gonadotropin-releasing hormone (GnRH) antagonist protocol, it is necessary to reinforce contraceptive guidance assuming that luteinizing hormone surge is not detected by measurement of serum level and ovulation is not suppressed by GnRH antagonist.

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During controlled ovarian stimulation, a 34-year-old woman complained of right lower abdominal pain after the decision to retrieve oocytes. Ovarian torsion was suspected and confirmed, so aspiration of follicular fluid was performed prior to oocyte retrieval for volume reduction of the affected ovary. Two days after that, oocytes were successfully collected.

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Splicing factor 3b subunit 1 (SF3B1) is the most commonly mutated RNA splicing factor identified in myelodysplastic syndrome (MDS), chronic lymphocytic leukemia, and uveal melanoma. The mechanisms by which SF3B1 mutations promote malignancy are poorly understood. Here, we integrated pan-cancer RNA sequencing to identify mutant SF3B1-dependent aberrant splicing events with a positive CRISPR screen to prioritize alterations that functionally promote oncogenesis.

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Additional sex combs-like 1 (ASXL1), an epigenetic modulator, is frequently mutated in myeloid neoplasms. Recent analyses of mutant ASXL1 conditional knockin (ASXL1-MT-KI) mice suggested that ASXL1-MT alone is insufficient for myeloid transformation. In our previous study, we used retrovirus-mediated insertional mutagenesis, which exhibited the susceptibility of ASXL1-MT-KI hematopoietic cells to transform into myeloid leukemia cells.

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