
Mamiko Sakata-YanagimotoUniversity Hospital Medical Information Network | UMIN
Mamiko Sakata-Yanagimoto
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227
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Introduction
Publications
Publications (227)
BACKGROUND
Heart failure with preserved ejection fraction (HFpEF) is a major health concern. Pathological stimuli and interactions between cardiac fibroblasts (CFs) and other cell types may lead to cardiac fibrosis and diastolic dysfunction, which are hallmarks of HFpEF. Interstitial and perivascular cardiac fibrosis correlates with poor prognosis...
We retrospectively evaluated the impacts of using granulocyte colony‐stimulating factor (G‐CSF) and its timing on posttransplant outcomes for 9766 adults with acute myeloid leukemia (AML) between 2013 and 2022 using a Japanese database. We separately evaluated three distinct cohorts based on graft type: 3248 received bone marrow transplantation (BM...
Background
Primary central nervous system lymphoma (PCNSL) is a rare lymphoid malignancy. Systemic profiling of the PCNSL tumor microenvironment (TME) was previously conducted through gene expression analysis. We investigated the prognostic impact of TME on survival to establish novel prognostic biomarkers in PCNSL patients.
Methods
We analyzed ex...
Background: Based on the results of the POLARIX study (NCT03274492; Tilly et al. N Engl J Med 2022), polatuzumab vedotin in combination with rituximab plus cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) was approved in 2022 for the treatment of patients with previously untreated diffuse large B-cell lymphoma (DLBCL) in Japan. Currently,...
[Background] ABO-incompatibility is not thought to be a contraindication for allogeneic hematopoietic stem cell transplantation (allo-HSCT), although the clinical impacts are occasionally debated. Post-transplant pure red blood cell aplasia (p-PRCA) is a disorder of erythropoiesis during the post-transplant immune tolerance process and is a rare co...
Background: Recent studies have shown that the extent of T-cell infiltration strongly correlates with a low frequency of early relapse in patients with follicular lymphoma (FL). This suggests that a deeper understanding of T-cell heterogeneity and biology could lead to the development of novel FL biomarkers. Our previous single-cell RNA sequencing...
Background: Thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HCT), which can lead to increased mortality and impaired quality of life with prolonged transfusion dependency and high risk of bleeding. However, it is not clear how many patients survive without sufficient platelet recovery after a...
Subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) is a rare peripheral T‐cell lymphoma characterized by cutaneous lesions and immunologic manifestations. The five‐year survival rate of SPTCL has been reported to be over 80%, indicating a favorable prognosis. Recent studies have uncovered recurrent germline variants in HAVCR2, encoding an immun...
A 64-year-old woman presented with fine motor impairment in both hands. MRI revealed a contrast-enhanced lesion in the medulla oblongata. Lymphoid cells with abnormal blebs were observed and a CD4+/CD8+ double positive (DP) T cell population was detected by flow cytometry (FCM) in the bone marrow (BM) and the peripheral blood (PB). CLEC16A::IL2 fus...
Background
Hypomethylating agents, including azacytidine (AZA), are standard therapeutics for patients with high‐risk myelodysplastic syndromes (MDS), a group of myeloid neoplasms. However, treatment schedules are not unified in real‐world practice; in addition to the standard 7‐day (standard‐dose) schedule, shortened (reduced‐dose) schedules are a...
Background: Comprehensive gene mutation profiling of primary central nervous system lymphoma (PCNSL) revealed genomic abnormalities associated with the NFκB signaling pathway and immune escape (Chapuy B, et al. Blood 2016). Although this has led to advances in targeted therapy, there are only a few candidate biomarkers for diagnosis and prediction...
Background: The presence and role of follicular T-cell populations other than T follicular helper (Tfh) cells, such as T follicular regulatory (Tfr) and cytotoxic (Tfc) cells, are gaining increasing attention in certain pathological states. However, the ecosystem of follicular T cells in the tumor microenvironment (TME) has not been fully elucidate...
Introduction: Clonal hematopoiesis (CH) is an age-related change in which blood cells with somatic mutations are clonally expanded. CH is known to be a predisposing factor for various age-related diseases. However, the characteristics of blood cells with somatic mutations derived from CH at the single-cell level is not fully understood.
Objective:...
[Backgrounds]
Clonal hematopoiesis (CH) has been observed in over 20% of patients diagnosed with solid cancers, and it has been associated with a poor prognosis in most cases, with the exception of colorectal cancer (CRC) patients who tend to have a favorable prognosis. Among the various gene mutations detected in CH, TET2 mutations are particularl...
T follicular helper (TFH) cell lymphomas (TFHLs) are characterized by TFH-like properties and accompanied by substantial immune-cell infiltration into tumor tissues. Nevertheless, the comprehensive understanding of tumor-cell heterogeneity and immune profiles of TFHL remains elusive. To address this, we conducted single-cell transcriptomic analysis...
Graft failure and delayed hematopoietic recovery are the major limitations of cord-blood transplantation (CBT). Romiplostim, a thrombopoietin-receptor agonist, promotes megakaryopoiesis and multilineage hematopoiesis in aplastic anemia. The decreased number of hematopoietic stem cells in the early phase after CBT and aplastic anemia share certain c...
Objectives
Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporin A is the standard treatment for aplastic anemia (AA). However, the efficacy of repeated IST with rabbit ATG (rATG) as salvage therapy remains unclear in patients with relapsed or refractory AA.
Methods
We retrospectively evaluated the efficacy and safety o...
In the hematopoietic system of healthy individuals, a phenomenon called clonal hematopoiesis, in which cells acquired somatic mutations are replaced with aging, has been discovered. The frequency of clonal hematopoiesis is higher in patients with solid tumors, than normal individuals. In addition, it is thought that infiltration of inflammatory cel...
A 61-year-old female was referred to our hospital because of pancytopenia and febrile neutropenia. On admission, computed tomography showed mild hepatosplenomegaly and intra-abdominal abscess formation in the right pelvic region; however, no lymphadenopathy was found. Bone marrow (BM) examination showed severe fibrosis by silver staining. Several s...
Sequencing technology has identified aplastic anemia (AA) not only as an autoimmune bone marrow failure syndrome, but also as a clonal hematopoietic disease. Here, we present a case in which an ASXL1-mutated clone was predominantly expanded during the treatment of AA. A 58-year-old man with chronic glomerulonephritis on maintenance hemodialysis pre...
A 51-year-old man with the chief complaint of glove- and stocking-type dysesthesia for >3 years was diagnosed with Waldenström's macroglobulinemia (WM) based on IgM-type M-proteinemia, bone marrow infiltration of plasmacytoid B cells, multiple lymphadenopathies, and splenomegaly. A nerve conduction examination suggested demyelinating neuropathy. Se...
BACKGROUND
Because adult cardiomyocytes have little regenerative capacity, resident cardiac fibroblasts (CFs) synthesize extracellular matrix after myocardial infarction (MI) to form fibrosis, leading to cardiac dysfunction and heart failure. Therapies that can regenerate the myocardium and reverse fibrosis in chronic MI are lacking. The overexpres...
In this study, we herein describe a 47-year-old Japanese woman who manifested inheritable non-alcoholic steatohepatitis (NASH) and severe dyslipidemia. Interestingly, her NASH progression was ameliorated by treatment with a sodium–glucose co-transporter 2 (SGLT2) inhibitor. This inheritability prompted us to comprehensively decode her genomic infor...
Triple-negative essential thrombocythemia (ET) is a condition in which mutations in JAK2, CALR and MPL are all negative. Transformation to acute myeloid leukemia may occur during the course of ET, while B-acute lymphoblastic leukemia (B-ALL) is rare. We experienced a case diagnosed as B-ALL during the course of triple-negative ET. Notably, cytoredu...
Angioimmunoblastic T-cell lymphoma (AITL) is proposed to be initiated by age-related clonal hematopoiesis (ACH) with TET2 mutations, whereas the G17V RHOA mutation in immature cells with TET2 mutations promotes development of T follicular helper-like tumor cells. Here, we investigated the mechanism by which TET2-mutant immune cells enable AITL deve...
Vanishing bile duct syndrome (VBDS) is a rare hepatic disorder which leads to liver failure as a result of progressive destruction of the intrahepatic bile ducts. There are no treatment modalities for VBDS itself and severe hepatic dysfunction restricts the treatment of underlying diseases. We safely treated a case of classic Hodgkin lymphoma (HL)...
Angioimmunoblastic T-cell lymphoma (AITL) is an intractable type of T-cell lymphoma. We and others have identified that the p.Gly17Val RHOA mutation is specifically identified in AITL. We herein report a patient whose condition deteriorated, resulting from massive pericardial effusion one month after undergoing autologous transplantation for AITL....
Autoimmune and complement-related hematological side effects have been observed with messenger ribonucleic acid (mRNA) vaccines. Here, we report the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH). We reviewed the medical records of sevent...
Objective Graft failure (GF) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT). A standardized conditioning regimen and an appropriate graft source of salvage HSCT for GF have not yet been established. Some case series have shown good hematopoietic recoveries after salvage HSCT using a short-term reduced-intensity...
The activities of non-haematopoietic cells (NHCs), including mesenchymal stromal cells and endothelial cells, in lymphomas are reported to underlie lymphomagenesis. However, our understanding of lymphoma NHCs has been hampered by unexplained NHC heterogeneity, even in normal human lymph nodes (LNs). Here we constructed a single-cell transcriptome a...
According to the recently revised WHO classification, peripheral T-cell lymphomas (PTCL) can be classified into up to 30 subtypes. Because the majority of these subtypes were rare cancers, their pathophysiology was not well understood. However, technological advancements including multi-omics approaches such as genomic and gene expression analyses...
NUP98::DDX10 is a rare fusion gene associated with acute myeloid leukemia (AML), for which the prognosis and indication for allogeneic hematopoietic stem cell transplantation are unknown. A 48-year-old woman was diagnosed with AML harboring NUP98::DDX10. The results of quantitative RT-PCR of the fusion mRNA as a minimal residual disease (MRD) marke...
Immune cells harboring somatic mutations reportedly infiltrate cancer tissues in patients with solid cancers and accompanying clonal hematopoiesis. Loss-of-function TET2 mutations are frequently observed in clonal hematopoiesis in solid cancers. Here, we evaluated activity of Tet2-deficient immune cells in tumor tissues using a mouse lung cancer mo...
It is believed that immune responses are different between individuals and at different times. In addition, personal health histories and unique environmental conditions should collectively determine the present state of immune cells. However, the cellular and molecular system mechanisms underlying such heterogeneity remain largely elusive. In this...
Other iatrogenic immunodeficiency‐associated lymphoproliferative disorders (OIIA‐LPDs) occur in patients receiving immunosuppressive drugs for autoimmune diseases; however, their clinicopathological and genetic features remain unknown. In the present study, we analysed 67 patients with OIIA‐LPDs, including 36 with diffuse large B‐cell lymphoma (DLB...
Inflammation, especially chronic inflammation, plays a pivotal role in tumorigenesis and metastasis through various mechanisms and is now recognized as a hallmark of cancer and an attractive therapeutic target in cancer. In this review, we discuss recent advances in molecular mechanisms of how inflammation promotes tumorigenesis and metastasis and...
E7777 is a recombinant cytotoxic fusion protein composed of the diphtheria toxin fragments A and B and human interleukin‐2. It shares an amino acid sequence with denileukin diftitox, but has improved purity and an increased percentage of active monomer. We conducted a multicenter, single‐arm phase 2 study of E7777 in patients with relapsed or refra...
Cytokine release syndrome (CRS), occurring in more than 70% of HLA-haploidentical hematopoietic stem-cell transplantations with post-transplant cyclophosphamide (PT/CY-haplo), can lead to hemodynamic instability and worsen clinical outcomes. A calcineurin inhibitor is initiated after cyclophosphamide administration in the commonly used PT/CY regime...
Peripheral T‐cell lymphomas (PTCL) are a heterogeneous group of blood cancers with varying pathological and clinical features. In this chapter the authors describe several mouse lines established for angioimmunoblastic T‐cell lymphoma (AITL), anaplastic large‐cell lymphoma (ALCL), adult T‐cell leukemia/lymphoma (ATLL), cutaneous T‐cell lymphoma (CT...
Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) includes various diseases. Attempts have been made to identify distinct properties of disease within the PTCL, NOS classification and evaluate their significance to prognosis. Comprehensive gene expression analysis and evaluation of genomic abnormalities have successfully identified sp...
Follicular T-cell lymphoma (FTCL), one of the nodal T-cell lymphomas with T follicular helper (T
FH
) phenotype, is an uncommon disease. The diagnosis of FTCL is challenging on the distinction from the morphological mimics mostly exemplified by follicular lymphoma. Here, we described a case of FTCL that mimicked lymphocyte-rich classic Hodgkin lymp...
A 50-year-old man demonstrated markedly increased number of white blood cells, anemia, severe splenomegaly, and bleeding tendency. Bone marrow analysis revealed remarkable hypercellularity; dysplasia in multilineage cells, including megakaryocytes; and fibrosis. He was eventually diagnosed with triple-negative myelofibrosis. A massive hematoma deve...
Bing-Neel syndrome (BNS), which presents with a variety of neurological complications, is a rare manifestation of the lymphoplasmacytic lymphoma (LPL) and is characterized by the infiltration of LPL cells into the central nervous system. In this study, we report the case of a patient with BNS, which was confirmed by detecting MYD88 L265P mutation i...
Eltrombopag, a thrombopoietin receptor agonist, is used for the treatment of idiopathic thrombocytopenic purpura (ITP) and aplastic anemia. We developed a high‐performance liquid chromatography (HPLC) assay for the determination of serum eltrombopag concentration in ITP patients. An aliquot of a serum sample spiked with diclofenac as the internal s...
Immunosuppressive therapy (IST) is the first-line treatment for young patients with severe aplastic anemia (AA) when a human leucocyte antigen (HLA)-matched related donor (MRD) is unavailable. Fulminant AA (FAA) is defined as AA with a complete absence of neutrophils at presentation and no response to granulocyte-colony stimulating factor (G-CSF) t...
In situ mantle cell neoplasia (isMCN) and leukemic non-nodal mantle cell lymphoma (nnMCL) are classified as an indolent subtype of mantle cell lymphoma (MCL). The tumor cells of isMCN are restricted to the inner layer of the lymphoid tissue mantle zone, exhibiting an in situ pattern histologically. On the other hand, nnMCL is distributed in the per...
Activating mutations in the Vav guanine nucleotide exchange factor 1 (VAV1) gene are reported in various subtypes of mature T-cell neoplasms (TCN). However, oncogenic activities associated with VAV1 mutations in TCN remain unclear. To define them, we established transgenic mice expressing VAV1 mutants cloned from human TCN. Although we observed no...
It has been nearly half a century since angioimmunoblastic T-cell lymphoma (AITL) was characterized in the early 1970’s. Our understanding of the disease has dramatically changed due to multiple discoveries and insights. One of the key features of AITL is aberrant immune activity. Although AITL is now understood to be a neoplastic disease, patholog...
Follicular T‐cell lymphoma (FTCL) is considered to originate from follicular helper T‐cell (Tfh) cells. Angioimmunoblastic T‐cell lymphoma (AITL) and peripheral T‐cell lymphomas with the Tfh phenotype, derived from Tfh cells, often harbor RHOA G17V mutation. We investigated whether RHOA mutations affect the clinicopathological features of FTCL. We...
Loss-of-function mutations in ten-eleven translocation-2 (TET2) are recurrent events in acute myeloid leukemia (AML) as well as in preleukemic hematopoietic stem cells (HSCs) of age-related clonal hematopoiesis. TET3 mutations are infrequent in AML, but the level of TET3 expression in HSCs has been found to decline with age. We examined the impact...
Recurrent hotspot (p.Gly17Val) mutations in RHOA encoding a small GTPase, together with loss-of-function mutations in TET2 encoding an epigenetic regulator, are genetic hallmarks of angioimmunoblastic T-cell lymphoma (AITL). Mice expressing the p.Gly17Val RHOA mutant on a Tet2-null background succumbed to AITL-like T-cell lymphomas due to deregulat...
A 46-year-old man who had previously undergone open surgery for renal cell carcinoma (RCC) developed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL). After the induction therapy, he achieved complete molecular remission. However, fever and bilateral buttock pain continued during the consolidation therapy. 18F-fluorodeoxygluco...
Epstein‐Barr virus (EBV)‐positive B cells have been detected in 66%‐86% of patients with angioimmunoblastic T‐cell lymphoma (AITL). However, it remains controversial whether EBV status has an impact on the survival of patients with AITL. In this study, we aimed to reevaluate the impact of EBV on the clinicopathological characteristics of AITL. In p...
Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) is a diagnosis of exclusion, being the most common entity in mature T-cell neoplasms, and its molecular pathogenesis remains significantly understudied. Here, combining whole-exome and targeted-capture sequencing, gene-expression profiling, and immunohistochemical analysis of tumor sam...
Background: Bone marrow (BM) fibrosis is common in both myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), its pathogenesis remains unclear. It is also unknown whether and how the pathophysiology of BM fibrosis in MDS and MPN are similar or different, while it is anticipated that altered BM microenvironment plays a key role.
Me...
[Background] Patients treated with immunosuppressive drugs for autoimmune diseases may suffer "other iatrogenic immunodeficiency-associated lymphoproliferative disorders" (OIIA-LPD). Some OIIA-LPDs regress after drug withdrawal but others need cytotoxic chemotherapy. However, the factors associated with a response to drug cessation remain unknown....
Background: E7777 is a recombinant cytotoxic fusion protein composed of diphtheria toxin fragments A, B and human interleukin-2. The amino acid sequence of E7777 is the same as that of denileukin diftitox, approved in the USA for treatment of persistent or recurrent CD25-positive cutaneous T-cell lymphoma in 1999, but the purity of E7777 is improve...
Background: VAV1 is known as an important mediator of T-cell receptor (TCR) signaling through its guanine exchange factor (GEF)-dependent and independent functions. Recent studies identified activating VAV1 mutations in several types of T-cell malignancies including peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), angioimmunoblastic...
Cell-free DNA (cfDNA) analysis to detect circulating tumor DNA has been focused in monitoring of malignant lymphomas. However, clonal hematopoiesis of indeterminate potential (CHIP)-associated mutations also can be detected by cfDNA analysis. Our aim is to investigate the origin of mutations detected in cfDNA among B-cell lymphoma patients. MYD88/C...
Notch signaling plays pivotal roles in both hematopoietic stem/progenitor and their niche cells. Myeloproliferative phenotypes are induced by disruption of Notch signaling in non‐hematopoietic bone marrow (BM) cells. Nestin‐expressing cells in the BM reportedly represent a component of the hematopoietic stem cell niche. We established mice in which...
Nestin-expressing stromal cells (NESCs) and Schwann cells in the bone marrow (BM) play crucial roles as a niche for normal hematopoietic stem cells in mice. It has been reported that both types of cells are decreased in myeloproliferative neoplasms in patients and also in a mouse model, whereas an increase in NESCs was reported in acute myeloid leu...
A 38-year-old woman with aggressive clinical course of chronic lymphocytic leukemia (CLL) was treated with 8 courses of R-CHOP. Clinical remission was achieved, while B-cell clonality remained. Allogeneic hematopoietic stem cell transplantation was performed with reduced intensity conditioning (fludarabine and 2-Gy total body irradiation). However,...