血液科学(英文)最新文献

[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.

Infections are frequent complications in patients with hematological disorders, and pathogen diagnosis remains challenging. Metagenomic next-generation sequencing (mNGS) is an unbiased high-throughput technology that has been widely applied in the diagnosis of infectious diseases. However, to date, there are no established international guidelines or expert consensuses regarding the use of mNGS to diagnose infections in patients with hematologic disorders. The Anti-Infection Study Group of the Chinese Society of Hematology invited experts in the fields of hematology, microbiology, and mNGS technology to draft an expert consensus focused on clinical indications, sample collection, quality control, and interpretation of results. This consensus will likely contribute to clarifying the medical indications for mNGS testing, optimizing the interpretation of reports, and becoming an inspiration for global practice.