Outcomes of patients aged 70 years or younger with aggressive ATL at core hospitals for ATL treatment in Tokyo.

Adult T-cell leukemia-lymphoma (ATL) is one of the most intractable peripheral T-cell neoplasms caused by human T-cell leukemia virus type I (HTLV-1) infection. Recently, the incidence of HTLV-1 infection and ATL has increased in non-endemic metropolitan areas in Japan. This retrospective study evaluated the clinical features and outcomes of patients with aggressive ATL aged 70 years or younger treated at a core hospital in Tokyo between 2004 and 2016.

Elaidic acid drives cellular senescence and inflammation via lipid raft-mediated IL-1R signaling.

Fatty acids (TFAs) have been associated with various inflammatory diseases, including atherosclerosis and metabolic syndrome, such as metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH). However, the underlying mechanism remains unclear. Here, we show that in response to DNA damage, elaidic acid (EA), a most common TFA, amplifies interleukin-1 receptor (IL-1R) signaling, leading to the promotion of cellular senescence and senescence-associated secretory phenotype (SASP).

Bridging therapy with valemetostat to allogeneic hematopoietic cell transplantation for adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus-1. Patients diagnosed with aggressive ATL have a poor prognosis. As response duration to conventional multiagent chemotherapy is short, upfront allogeneic hematopoietic cell transplantation (allo-HCT) is recommended.

Risk of acute graft-versus-host disease in recipients with IL-10 promoter polymorphism rs1800872, but not IL-10 receptor β polymorphism rs2834167, after single-unit cord blood transplantation.

The function of Interleukin-10 (IL-10) is affected by polymorphisms in the promoter region of the IL-10 gene and IL-10 receptor β (IL-10Rβ), which are associated with acute and chronic graft-versus-host disease (GVHD) in allogeneic hematopoietic cell transplantation from adult donors. We investigated the effect of recipient and donor IL-10 (rs1800872) and IL-10Rβ (rs2834167) polymorphisms on outcomes in adults who underwent cord blood transplantation (CBT) at our institution. A total of 158 recipients and 136 donors were included in this study.

Whole-genome sequencing of myeloproliferative neoplasms revealed dynamic clonal changes in the fibrotic or leukemic transformation and novel FOXP1 mutations in the fibrotic transformation.

Myeloproliferative neoplasms (MPNs) are characterized by clonal proliferation of hematopoietic stem cells, which can lead to secondary myelofibrosis or acute myeloid leukemia. We explored the changes in genomic alterations during MPN transformation using whole-genome sequencing of samples from both the chronic and fibrotic or leukemic phases of 20 patients. We identified FOXP1 mutations in 3 of 14 (21.

Tracking clusterin expression in hematopoietic stem cells reveals their heterogeneous composition across the life span.

Hematopoietic stem cells (HSCs) exhibit significant age-related phenotypic and functional alterations. Although single-cell technologies have elucidated age-related compositional changes, prospective identification of aging-associated HSC subsets has remained challenging. In this study, using clusterin (Clu)-green fluorescent protein (GFP) reporter mice, we demonstrated that Clu expression faithfully marks age-associated myeloid/platelet-biased HSCs throughout life.

A novel stroma-dependent leukemia cell line from a patient with mixed-phenotype acute leukemia with Ph chromosome and PAX5 mutation.

Mixed phenotype acute leukemia (MPAL) is a rare and aggressive form of leukemia with a poor prognosis and no established treatment. In this study, we established a novel leukemic cell line, JMPAL-1, from a specimen of a 69-year-old patient with Philadelphia chromosome-positive MPAL. Flow cytometry showed that JMPAL-1 expresses B-cell markers but not myeloperoxidase.

Prognosis of aggressive adult T-cell leukemia/lymphoma with central nervous system infiltration and utility of CD7 versus CADM1 flowcytometric plots of cerebrospinal fluid.

The prognosis of adult T-cell leukemia/lymphoma (ATL) with primary central nervous system (CNS) involvement has been unclear since the advent of new therapies. Recently, we have shown that flow cytometric CD7/CADM1 analysis of CD4 + cells (HAS-Flow) is useful to detect ATL cells that are not morphologically diagnosed as ATL cells. We investigated the role of CNS involvement in ATL using cytology and HAS-Flow by analyzing cerebrospinal fluid (CSF) from 73 aggressive ATL cases.

Higher relapse and worse overall survival in recipients with CTLA-4 AA genotype of rs231775 following single-unit cord blood transplantation in adults.

We retrospectively investigated the impact of CTLA-4 polymorphism on outcomes for adult patients who received single-unit cord blood transplantation (CBT) at our institution. CTLA-4 genotyping was performed using real-time polymerase chain reaction with the TaqMan SNP genotyping assay for rs231775. This study included 143 recipient-donor pairs.

Common progenitor origin for Rosai-Dorfman disease and clear cell sarcoma.

Histiocytic neoplasms (HNs) in adults have been reported to be associated with a high prevalence of coexisting haematological and solid malignancies. While a proportion of coexisting HNs and haematological malignancies share identical genetic alterations, the genetic association between HNs and solid malignancies has scarcely been reported. We report a case of Rosai-Dorfman disease (RDD) complicated by coexisting clear cell sarcoma (CCS).

Recipient IL-17A polymorphism rs2275913 is associated with acute graft-versus-host disease after single-unit cord blood transplantation.

Background: Interleukin-17 (IL-17) is elevated in human inflammatory and autoimmune diseases. The polymorphism in the promoter region of the IL-17 A gene is associated with susceptibility to several inflammatory diseases, including acute graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation from adult donors. However, the impacts of IL-17 A polymorphism on cord blood transplantation (CBT) outcomes remain unclear.

Flow cytometric profiles with CD7 and CADM1 in CD4+ T cells are promising indicators for prognosis of aggressive ATL.

Adult T-cell leukemia/lymphoma (ATL) is a poor prognosis hematological malignancy originating from human T-cell leukemia virus 1 (HTLV-1)-infected CD4+ T cells. Flow cytometric plots of CADM1 and CD7 in CD4+ T cells are useful for separating HTLV-1-uninfected T cells and ATL cells. They are indicators of clonal evolution of HTLV-1-infected cells and disease progression of asymptomatic carriers or indolent ATL.

Pathogenicity Prediction of Gene Fusion in Structural Variations: A Knowledge Graph-Infused Explainable Artificial Intelligence (XAI) Framework.

When analyzing cancer sample genomes in clinical practice, many structural variants (SVs), other than single nucleotide variants (SNVs), have been identified. To identify driver variants, the leading candidates must be narrowed down. When fusion genes are involved, selection is particularly difficult, and highly accurate predictions from AI is important.

Analyzing factors affecting positivity in drive-through COVID-19 testing: a cross-sectional study.

Background: Demand for COVID-19 testing prompted the implementation of drive-through testing systems. However, limited research has examined factors influencing testing positivity in this setting.

Methods: From October 2020 to March 2023, a total of 1,341 patients, along with their clinical information, were referred from local clinics to the Sasebo City COVID-19 drive-through PCR center for testing.

[Durable remission of T-cell prolymphocytic leukemia with CLEC16A::IL2 after allogeneic hematopoietic stem cell transplantation].

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).

Refractory Intestinal Behçet-Like Disease Associated with Trisomy 8 Myelodysplastic Syndrome Resolved by Parenteral Nutrition.

Intestinal Behçet disease (BD), associated with myelodysplastic syndrome (MDS), is often refractory to treatment. An 80-year-old man with trisomy 8 MDS (refractory anemia) developed intermittent fever. Despite investigations to exclude infectious disease, autoimmune disease, and malignancy as the cause of the fever, the etiology could not be determined.

Ceramide synthase CERS4 gene downregulation is associated with KRAS mutation in colorectal cancer.

Ceramide, the central molecule in sphingolipid synthesis, is a bioactive lipid that serves as a regulatory molecule in the anti-inflammatory responses, apoptosis, programmed necrosis, autophagy, and cell motility of cancer cells. In particular, the authors have reported differences in sphingolipid content in colorectal cancer tissues. The associations among genetic mutations, clinicopathological factors, and sphingolipid metabolism in colorectal cancer (CRC) have not been investigated.

expression and DNA homologous recombination repair factors in lung cancers with a high-grade fetal adenocarcinoma component.

Background: High-grade fetal adenocarcinoma of the lung (H-FLAC) is a rare variant of pulmonary adenocarcinoma. Our previous study showed a high frequency of KMT2C mutations in lung cancers with an H-FLAC component, showing that KMT2C dysfunction may be associated with the biological features of H-FLACs.

Methods: In this study, we performed RNA sequencing and immunohistochemical analysis to identify the differentially expressed genes and corresponding pathways associated with H-FLACs, compared with common adenocarcinomas.

Genetic analysis of low-grade adenosquamous carcinoma of the breast progressing to high-grade metaplastic carcinoma.

Purpose: Low-grade adenosquamous carcinoma (LGASC) is a rare type of metaplastic carcinoma of the breast (MBC) with an indolent clinical course. A few LGASC cases with high-grade transformation have been reported; however, the genetics underlying malignant progression of LGASC remain unclear.

Methods: We performed whole-genome sequencing analysis on five MBCs from four patients, including one case with matching primary LGASC and a lymph node metastatic tumor consisting of high-grade MBC with a predominant metaplastic squamous cell carcinoma component (MSC) that progressed from LGASC and three cases of independent de novo MSC.

Clinical and prognostic features of Langerhans cell histiocytosis in adults.

Langerhans cell histiocytosis (LCH) is a rare disease characterized by clonal expansion of CD1a CD207 myeloid dendritic cells. The features of LCH are mainly described in children and remain poorly defined in adults; therefore, we conducted a nationwide survey to collect clinical data from 148 adult patients with LCH. The median age at diagnosis was 46.