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.

Post-transplant transient abnormal myelopoiesis evolving from a GATA1 mutant clone in umbilical cord blood.

Transient abnormal myelopoiesis (TAM) generally affects newborns with Down syndrome and is associated with constitutional trisomy 21 and a somatic GATA1 mutation. Here we describe a case of TAM which evolved after umbilical cord blood transplantation (UCBT), whose origin was identified as a GATA1 mutation-harboring clone in umbilical cord blood (UCB) by detailed genetic analyses. A 58-year-old male who received UCBT for peripheral T-cell lymphoma presented progressive anemia and thrombocytopenia, and leukocytosis with blast cells in the peripheral blood (PB).

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.

Rewired chromatin structure and epigenetic gene dysregulation during HTLV-1 infection to leukemogenesis.

Human T-cell leukemia virus type 1 (HTLV-1) broadly impacts host genes, affecting the infected cell population and inducing the development of a disease with a poor prognosis, adult T-cell leukemia-lymphoma (ATL). This study aimed to provide a comprehensive epigenomic characterization of the infected cell population and evaluated the transcriptome and chromatin structures of peripheral blood cells in HTLV-1-infected individuals using RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin sequencing (ATAC-seq). The infected cells showed significant changes in gene expression patterns from the polyclonal stage and before ATL onset while demonstrating similarities to tumor-forming ATL cells.

Translational Research on Azacitidine Post-Remission Therapy of Acute Myeloid Leukemia in Elderly Patients (QOL-ONE Trans-2).

The achievement of complete remission (CR) is crucial for acute myeloid leukemia (AML) patients undertaking curative therapy, but relapse often occurs within months, highlighting the need for strategies to prolong disease-free survival (DFS). Our phase III study compared the efficacy and safety of azacitidine (AZA) to best supportive care (BSC) in elderly AML patients who achieved CR following intensive induction and consolidation therapy. This ancillary study (QOL-ONE Trans-2) evaluated biological changes in bone marrow using Next-Generation Sequencing (NGS).

Sexual transmission of HTLV-1 resulting in uveitis with short-term latency and low proviral load.

Human T-cell Lymphotropic Virus Type 1 (HTLV-1) is traditionally linked to severe conditions such as adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy, and HTLV-1 uveitis, with vertical transmission, particularly mother to child thorough breastfeeding, considered the primary route. Despite efforts to reduce vertical transmission through antenatal screening in Japan, horizontal transmission has contributed to the rising prevalence of HTLV-1 in metropolitan areas. This case reports the youngest documented instance of HTLV-1 uveitis resulting from horizontal transmission through sexual contact in an 18-year-old woman.

Levels of C-Reactive Protein and Body Temperature Elevation During Neutropenia Predict Engraftment and Non-Relapse Mortality for Unrelated Single-Unit Cord Blood Transplantation in Adults.

Cord blood transplantation (CBT) presents unique challenges related to inflammation during neutropenia, such as mucosal damage, infections, and the potential development of pre-engraftment syndrome or pre-engraftment immune reaction. These factors can contribute to significant inflammation and infection shortly after CBT. However, the effect of severe inflammation during neutropenia, specifically elevated C-reactive protein (CRP) level and body temperature, on post-transplant outcomes after CBT remains unclear.

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).

Comparison of disease and risk classifications of AML before and after incorporation of NGS analysis of bone marrow samples.

Mutation profiling by next-generation sequencing (NGS) has facilitated understanding of the molecular pathogenesis of acute myeloid leukemia (AML), and has been incorporated into the new disease classification (International Consensus Classification; ICC) and risk classification (European LeukemiaNet [ELN] 2022; ELN2022). We compared disease subtypes between the previous disease classification (4th edition of the WHO classification; WHO-4) and the ICC in 91 patients with AML diagnosed at our institution. We also compared disease risk classifications using the previous risk classification (ELN2017) and the ELN2022.

Inhibition of TOPORS ubiquitin ligase augments the efficacy of DNA hypomethylating agents through DNMT1 stabilization.

DNA hypomethylating agents (HMAs) are used for the treatment of myeloid malignancies, although their therapeutic effects have been unsatisfactory. Here we show that CRISPR-Cas9 screening reveals that knockout of topoisomerase 1-binding arginine/serine-rich protein (TOPORS), which encodes a ubiquitin/SUMO E3 ligase, augments the efficacy of HMAs on myeloid leukemic cells with little effect on normal hematopoiesis, suggesting that TOPORS is involved in resistance to HMAs. HMAs are incorporated into the DNA and trap DNA methyltransferase-1 (DNMT1) to form DNA-DNMT1 crosslinks, which undergo SUMOylation, followed by proteasomal degradation.

Prognostic Value of the Pretransplant Fibrosis-4 Index on Non-Relapse and Overall Mortality following Unrelated Single-Unit Cord Blood Transplantation in Adults.

Introduction: The fibrosis-4 (FIB-4) index is a noninvasive marker of liver fibrosis. The FIB-4 index predicts poor outcomes in patients with hepatic and non-hepatic diseases. However, the association of the FIB-4 index with mortality and liver-related clinical outcomes following cord blood transplantation (CBT) is unclear.

Modelling and drug targeting of a myeloid neoplasm with atypical 3q26/MECOM rearrangement using patient-specific iPSCs.

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.

Small cell pattern of ALK-negative anaplastic large cell lymphoma with double-hit rearrangements of and .

In ALK-negative anaplastic large cell lymphoma (ALCL), gene rearrangements of and are considered mutually exclusive. The former predicts a favorable prognosis, while the latter is generally unfavorable. We report the first case of ALK-negative ALCL in a leukemic phase with small cell pattern transformation, harboring double-hit rearrangements of the gene by inv(6)(p25q21) and gene by TBL1XR1-TP63 inversion.

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.

Influence of interruption of oral mycophenolate mofetil for graft-versus-host disease prophylaxis on outcomes after single cord blood transplantation.

Mycophenolate mofetil (MMF), in combination with a calcineurin inhibitor, is used as the prophylaxis for graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). Compared to intravenous methotrexate (MTX), MMF is associated with a lower incidence of mucositis and shorter time for hematopoietic engraftment but comparable incidence of acute GVHD, resulting in the preferred use of MMF for GVHD prophylaxis in elderly patients or those undergoing cord blood transplantation (CBT). Although several studies have evaluated the clinical impact of MTX omission due to toxicity after allogeneic HCT, the impact of oral MMF interruption for GVHD prophylaxis on transplant outcomes remains unclear.

Cellular and humoral immunogenicity against SARS-CoV-2 vaccination or infection is associated with the memory phenotype of T- and B-lymphocytes in adult allogeneic hematopoietic cell transplant recipients.

We conducted a cross-sectional study to evaluate cellular and humoral immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination or infection and examine how lymphocyte subpopulations in peripheral blood correlate with cellular and humoral immunogenicity in adult allogeneic hematopoietic cell transplantation (HCT) recipients. The median period from SARS-CoV-2 vaccination or infection to sample collection was 110.5 days (range, 6-345 days).

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.