血液科学(英文)最新文献

Haplo-fever (HF) is a form of non-infectious fever that occurs shortly after haploidentical (HID) hematopoietic stem cell transplantation (HSCT). Its clinical significance, risk factors, and pathophysiology, particularly in the context of anti-thymocyte globulin (ATG)-based prophylaxis for graft-versus-host disease (GvHD), remain largely unknown. Here, we retrospectively analyzed clinical data from 143 consecutive HID HSCT recipients. Patients with HF exhibited a higher incidence of chronic GvHD, a lower risk of measurable residual disease recurrence, and improved event-free survival, particularly among those receiving ATG-based acute GvHD prophylaxis. Identified risk factors for HF included higher infused doses of CD34⁺ cells, mononucleated cells, CD3⁺ T cells, and CD4⁺ memory T cells. At 90 days post-transplant, patients with HF demonstrated elevated absolute numbers of CD4⁺ memory T cells and activated CD4⁺ and CD8⁺ T cells. RNA sequencing of peripheral blood CD3⁺ T cells at day 2 post-transplant revealed transcriptional signatures of T-cell activation and an abundance of activated CD4⁺ memory T cells as hallmarks of HF. Using multiple complementary approaches, we demonstrated the impact of HF on transplant outcomes, identified its risk factors, and elucidated the underlying cellular and molecular mechanisms.

Single-cell chromatin accessibility analysis enables high-resolution dissection of regulatory elements and gene regulatory mechanisms. However, standardized and comprehensive analysis workflows remain limited. In this study, we present a streamlined pipeline for analyzing single-cell chromatin accessibility data. The workflow begins with data preprocessing using single-cell assay for transposase-accessible chromatin (scATAC)-pro or Cell Ranger ATAC, followed by peak calling with MACS2 and differential accessibility analysis to detect open chromatin regions and perform differential accessibility analysis to highlight regulatory differences among cell populations. Transcription factor activity is then inferred using chromVAR, incorporating motif enrichment and footprinting analysis. Finally, SCENIC+ is applied to reconstruct transcriptional regulatory networks, enabling in-depth exploration of epigenetic mechanisms at the single-cell level. This integrative approach offers a robust framework for decoding the regulatory landscape and understanding cellular heterogeneity in complex biological systems.

[This corrects the article DOI: 10.1097/BS9.0000000000000236.].

FLT3-ITD, NPM1, and DNMT3A mutations are common in acute myeloid leukemia (AML). However, the prognostic role of FLT3-ITD combined with NPM1 and/or DNMT3A mutations after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. In this retrospective study, 100 AML patients were selected from a cohort of 1292 who underwent allo-HSCT between 2014 and 2024. Patients were stratified by co-mutation profiles to compare prognosis, identify predictors of survival and relapse, and assess the efficacy of maintenance therapy. With a median follow-up after allo-HSCT of 16.1 months (interquartile range 8.1-26.2), 2-year overall survival (OS) rates were 65.1%, 68.3%, and 67.1%; leukemia-free survival (LFS) rates were 61.6%, 68.7%, and 63.2%; and cumulative incidence of relapse (CIR) rates were 16.9%, 12.5%, and 15.8%, respectively. No significant differences were observed among the groups. In multivariate analysis with FLT3 inhibitor as a time-dependent covariate, FLT3-ITD measurable residual disease (MRD) positivity prior to allo-HSCT was independently associated with inferior OS (hazard ratio [HR] = 3.51, 95% CI 1.34-9.17), LFS (HR = 3.05, 95% CI 1.26-7.35), and CIR (HR = 4.78, 95% CI 1.55-14.81). In contrast, posttransplant maintenance therapy with FLT3 inhibitors independently conferred a favorable impact on OS (HR = 0.15, 95% CI 0.03-0.66), LFS (HR = 0.24, 95% CI 0.07-0.83), CIR (HR = 0.10, 95% CI 0.01-0.66), and nonrelapse mortality (NRM) (HR = 0.25, 95% CI 0.07-0.89). In conclusion, FLT3-ITD-based double or triple mutations showed comparable posttransplant outcomes. FLT3-ITD MRD status and early maintenance therapy were key prognostic and therapeutic factors.

Clustered regularly interspaced short palindromic repeats (CRISPR) screens represent a transformative force in biological discovery, enabling the unbiased interrogation of gene function in a wide range of applications. Traditional screening approaches predominantly hinge on cell fitness or established markers, which inherently constrain their abilities for unbiased biological discovery. By contrast, single-cell CRISPR screening technologies, which combine pooled CRISPR screens with an array of sophisticated single-cell omics platforms, permit comprehensive profiling of the transcriptome and epigenome following individual genetic manipulations within complex cellular ecosystems. Over the past decade, a panoply of single-cell CRISPR platforms has emerged, each tailored to address specific experimental challenges. Iterative refinements in protocols have bolstered precision, scalability, and reproducibility, thereby enormously advancing functional genomics and translational research. However, technical obstacles such as perturbation efficiency, scalability, and data integration persist, necessitating cross-disciplinary collaboration and innovation. As single-cell CRISPR platforms evolve to incorporate spatial resolution, multi-omics integration, and AI-guided design, they are poised to bridge the gap between genetic perturbation and system-level interpretation. Here, we summarize recent advances in single-cell CRISPR technologies, outline their applications, and provide a comparative framework to guide platform selection (Perturb-seq, CROP-seq, ECCITE-seq, Direct-seq, and Mosaic-seq).

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a curative therapy for hematological malignancies, with T-cell immune reconstitution playing a pivotal role in determining clinical outcomes. This review comprehensively illustrates the processes and influencing factors of T-cell recovery post-HSCT, highlighting the dual pathways of reconstitution: thymus-independent peripheral expansion and thymus-dependent central regeneration. Key factors such as recipient and donor age, human leukocyte antigen disparity, conditioning regimens, immunosuppressive therapies, cytomegalovirus reactivation, and graft-versus-host disease (GVHD) significantly impact T-cell reconstitution dynamics and functional recovery. Furthermore, the article discusses the critical balance between graft-versus-leukemia (GVL) effects and GVHD, emphasizing how T-cell exhaustion, inhibitory receptor overexpression, and clonal dynamics contribute to relapse. Emerging technologies, including single-cell multi-omics, spatially resolved proteomics, T cell receptor repertoire analysis, and artificial intelligence-driven modeling, are explored for their potential to deepen mechanistic understanding and enable personalized therapeutic strategies. Ultimately, enhancing T-cell reconstitution through optimized transplantation protocols and targeted interventions is essential for reducing complications and improving long-term survival.

The yolk sac drives vertebrate embryonic hematopoiesis through primitive hematopoiesis and endothelial-to-hematopoietic transition (EHT) waves. However, dynamic cellular and molecular changes during EHT of the yolk sac remain to be elucidated. We built a comprehensive atlas of early endothelial and hematopoietic development in the yolk sac by integrating single-cell transcriptomic data from mouse embryos (E6.75-E11.0). Focusing on the yolk sac (E7.5-E9.5), we established a refined atlas capturing key cell populations of EHT in the yolk sac. This enabled the identification of distinct hemogenic endothelial cell (HEC) subpopulations and revealed 2 fundamentally distinct waves of yolk sac hemogenesis via EHT that differed in temporal emergence, cellular origin, molecular signature, and lineage bias. The first EHT wave, emerging around E8.0, originated from primordial endothelial cells and exhibited a bias toward the generation of erythromyeloid progenitors. In contrast, the second EHT wave, emerging around E8.5, originated from maturing yolk sac endothelial cells, expressed key intraembryonic HEC markers (Hlf, Nupr1, Gfi1), and showed a hematopoietic stem and progenitor cell fate bias. Furthermore, molecular dynamics analysis of the pseudo-trajectory during the 2 waves of EHT in mouse yolk sacs revealed different dynamic changes in several pathways, particularly the ribosome and metabolic pathways. The yolk sac endothelial and hematopoietic atlas is accessible from an interactive web server (https://lllab.shinyapps.io/ysshinyapp/). Collectively, this study provides novel insights into the multi-wave nature of yolk sac hematopoiesis, clarifies the fundamental principles of yolk sac EHT at a single-cell resolution, and offers potential guidance for in vitro blood cell regeneration strategies.