Congenital sideroblastic anemia (CSA) is a rare and heterogeneous disorder characterized by the presence of ring sideroblasts within the bone marrow. The underlying pathogenesis of CSA is predominantly attributed to defects in three major pathways: heme biosynthesis, iron-sulfur cluster biogenesis, and mitochondrial protein synthesis. The advent of next-generation sequencing technologies has facilitated the identification of numerous pathogenic gene mutations, offering valuable insights into the molecular mechanisms underlying CSA. Emerging therapeutic strategies, such as vitamin B6 supplementation, iron chelation therapy, hematopoietic stem cell transplantation, innovative agents including luspatercept, and gene-editing techniques, exhibit promising potential in managing anemia and reducing iron overload. This review summarizes genetic advances, pathophysiological mechanisms, and evolving treatments, underscoring the shift toward precision medicine in CSA management.

Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by clonal hematopoietic dysregulation, amplification of chronic inflammation, and progressive remodeling of the bone marrow fibrotic niche, clinically manifesting as bone marrow failure, splenomegaly, and systemic inflammatory symptoms. Although Janus kinase (JAK) inhibitors can alleviate symptom burden and reduce spleen size, they have limited capacity to eradicate malignant clones or reverse fibrosis. Allogeneic hematopoietic stem cell transplantation remains the only potentially curative option; however, its application is constrained by advanced age, comorbidities, unavailable donor, and transplant-related risks. Therefore, the development of disease-modifying therapeutic strategies has become a central focus in MF research. Chimeric antigen receptor T (CAR-T)-cell therapy has demonstrated robust efficacy across various hematologic malignancies. Its application in MF holds the potential not only to selectively eliminate malignant hematopoietic clones but also to modulate the immunosuppressive and profibrotic microenvironment through advanced cellular engineering, thereby enabling a dual therapeutic paradigm involving both clonal control and microenvironmental reprogramming. In this context, potential targets and pathways include CD123, myeloproliferative leukemia protein (MPL), fibroblast activation protein (FAP), the TGF-β signaling axis, the CXCR4-CXCL12 niche-regulatory axis, and molecules associated with myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). Future strategies may optimize both efficacy and safety through combinatorial approaches, including integration with JAK inhibitors, development of armored CAR-T constructs, and bridging to hematopoietic stem cell transplantation. Collectively, CAR-T-cell therapy offers a promising avenue for shifting MF management from symptomatic control toward true disease modification.

Glanzmann thrombasthenia (GT) is an inherited hemorrhagic disorder characterised by impaired platelet functions, manifested clinically as spontaneous bleeding. It is usually inherited in an autosomal recessive manner. Platelet dysfunction in patients with GT is caused by quantitative and/or qualitative deficiencies in αIIbβ3, which result from mutations in the genes encoding αIIbβ3. These genetic alterations lead to platelet dysfunction characterised by impaired fibrinogen binding capacity upon agonist stimulation, defective aggregation and spreading. While classical GT typically exhibits normal platelet counts and morphology, very rare mutations in ITGA2B (encoding αIIb) and/or ITGB3 (encoding β3) cause macrothrombocytopenia or increased platelet anisotropy (heterogeneity of platelet size and morphology). This type of mutation mainly localises in the membrane-proximal region of αIIbβ3 and is inherited in an autosomal dominant manner. This particular type of disorder is called ITGA2B/ITGB3-related macrothrombocytopenia and has been considered a subset of congenital macrothrombocytopenia. Current research suggests that gain-of-function mutations in ITGA2B or ITGB3 underlie the pathogenesis of most ITGA2B/ITGB3-related macrothrombocytopenia and mechanistically distinguish it from classical GT. However, recent reports have documented non-activating ITGB3 mutations that also cause macrothrombocytopenia, presenting a profound challenge to the mechanistic understanding of ITGA2B/ITGB3-related macrothrombocytopenia. This review summarises the reported cases of gain-of-function mutations in ITGA2B and ITGB3 associated with ITGA2B/ITGB3-related macrothrombocytopenia hitherto and discusses the potential molecular pathways contributing to the unique phenotypes in ITGA2B/ITGB3-related macrothrombocytopenia.

Multiple myeloma (MM) is a malignant hematological tumor characterized by the proliferation of monoclonal plasma cells, often accompanied by systemic complications such as bone destruction, renal dysfunction, and hypercoagulability. Plasma D-dimer, as a fibrinolytic marker, may be associated with disease activity. However, there are few reports on the application of plasma D-dimer in evaluating treatment efficacy in MM. This multicenter retrospective study aimed to evaluate the utility of plasma D-dimer levels in predicting treatment response in patients with MM. 160 patients with newly diagnosed MM were enrolled. Blood samples were collected from these patients during their first hospital visit and again after eight cycles of chemotherapy to measure D-dimer levels. This study explores the relationship between plasma D-dimer levels before and after treatment and patient clinical characteristics. Patients showed no statistically different plasma D-dimer levels at initial consultation across treatment-response groups: CR group (0.96 µg/mL [0.67–1.9]), PR group (0.88 µg/mL [0.56–1.39]), SD group (0.68 µg/mL [0.56–0.89]), and PD group (0.91 µg/mL [0.52–1.55]). After chemotherapy, both the absolute change (Dd) and percentage change (Ddp) in D-dimer levels showed significant differences among groups (p < 0.05). The CR and PR groups exhibited significantly greater reductions in D-dimer (Dd: -0.42 and − 0.40 µg/mL; Ddp: -45.2% and − 39.1%) compared to the PD group (Dd: 0.16 µg/mL; Ddp: 18.7%). Patients with overall response (OR) (CR and PR groups) had significantly greater decreases in both Dd and Ddp compared to no-response patients (PD and SD groups) (p < 0.001). Our results suggested that changes in plasma D-dimer levels before and after treatment may provide valuable insights for assessing chemotherapy efficacy in MM.

Platelet spreading and clot retraction, albeit both mediated by integrin outside-in signaling, lead to platelet shape changes in two opposite directions. The mechanisms by which these processes are regulated are not fully understood. Our previous study found that E726Q mutation in β3 integrin caused impaired spreading in Chinese hamster ovary (CHO) cells on immobilized fibrinogen.The current study further utilized knock-in mice bearing the β3E726Q mutation to explore the underlying mechanisms whereby the E726 residue differentially influences platelet spreading and clot retraction.Compared to wild type (WT) platelets, β3E726Q platelets displayed similar level of β3 expression but partially impaired fibrinogen binding associated with attenuated responses in platelet aggregation and P-selectin exposure. Notably, β3E726Q mutation resulted in defective platelet spreading but accelerated clot retraction concomitant with increased clot density. Functionally, β3E726Q mice displayed prolonged bleeding time and defective thrombogenesis in vitro and in vivo. Further mechanistic study showed that in β3E726Q platelets the activities of RhoA and Rac1 were significantly enhanced following thrombin stimulation, possibly due to reduced binding of Gα13 to the β3 cytoplasmic tail.Taken together, the β3E726 is a potential novel regulatory site that influences the direct interaction of β3 cytoplasmic tail with Gα13 and therefore the activity of downstream RhoA, a molecular switch that shifts platelet spreading into clot retraction.

Introduction Hematological malignancies (HM) are heterogeneous with complex pathophysiology. Glycans, the third major informational biopolymer, surpass nucleic acids and proteins in structural complexity and information density. As a prevalent post-translational modification, glycosylation serves as a functional readout of genetic variants and drives HM development. However, HM glycomics research is at an early stage compared to other omics fields. Therefore, we conducted the largest multi-center clinical study to date in the field of HM glycomics, mapping the total blood N-glycome (TBNG) landscape across HM subtypes and treatment phases. Methods Patients were enrolled from a multi-center observational clinical study registered with the Chinese Clinical Trial Registry (ChiCTR) (Registration number: ChiCTR2400089864). Participants were recruited from 8 medical centers. TBNG features in HM were investigated using retrospective samples and prospective longitudinal samples. The study was approved by the Medical Ethics Committee of the Affiliated Drum Tower Hospital of Nanjing University Medical School (IRB No. 2024-654-01) and conducted in accordance with the Declaration of Helsinki. Serum N-glycan profiling was performed using capillary electrophoresis. Serum N-glycan detection followed previously described methods (Su R et al. Hepatology 2025). Nine specific serum N-glycan peaks were identified per sample. Results TBNG analysis was performed on 979 HM patients from 8 centers (April 2016 - April 2024), including 348 MM (35.5%), 370 lymphoma (37.8%), and 261 acute leukemia (AL) (26.7%) cases. The retrospective cohort included 923 patients (94.3%) (samples only at diagnosis or a single post-treatment follow-up point) while the prospective longitudinal cohort included 56 patients (5.7%) (samples at diagnosis and complete remission (CR) follow-up). Analysis covered 1,035 samples: 641 at diagnosis (ND), 59 at PR/VGPR, 257 at CR, and 78 at relapse/refractory (R/R). Healthy controls (n=150) were included. Firstly, we identified distinct TBNG profiles differentiated HM types. All HM patients (MM, lymphoma, AL) showed elevated triantennary glycan Peak9 (NA3Fb) vs. controls (p < 0.0001). TBNG also correlated with subtypes and risk stratification. In MM, IgG type showed increases in two monogalactosyl N-glycans (Peak3 and Peak4, NG1A2F; p < 0.0001), IgA type showed increase in biantennary glycan Peak7 (NA2FB, p < 0.0001), and light chain (LC) type showed increase in Peak9 (p < 0.0001). In DLBCL, elevated Peak9 correlated with aggressiveness and tumor burden: higher in aggressive vs. indolent lymphomas (p=0.022), Group B vs. A (p=0.0002), and stage III/IV vs. I/II (p=0.018). These findings support TBNG's potential as a biomarker for HM diagnosis, subtyping, and risk stratification. More importantly, we observed that the above-mentioned characteristic glycan changes vary with different disease remission statuses. Retrospective analysis confirmed significant differences in TBNG between ND and CR states. For IgG MM, Peak3 and Peak4 significantly decreased at CR compared to ND (p < 0.0001). For IgA MM, Peak7 decreased at CR (p < 0.0001). For LC MM, Peak9 decreased at CR (p = 0.0002). DLBCL and AML patients showed decreases in Peak9 at CR (p = 0.0006). TBNG profile at CR tends to be closer to that of healthy individuals, while the R/R group exhibited TBNG characteristics more similar to the ND group. To validate the findings from the retrospective study, we conducted an additional analysis focusing on the longitudinal changes in N-glycan patterns before and after treatment in 56 patients. The prospective cohort results confirmed retrospective TBNG trends between ND and CR states, supporting TBNG's potential as a biomarker for treatment response and MRD monitoring. Conclusion Using the largest HM blood cohort analyzed glycomically to date, this study delineates the comprehensive TBNG landscape in real-world patients. The findings suggest that different disease entities, subtypes, and stages of HM exhibit characteristic TBNG alterations. Furthermore, these TBNG signatures dynamically change in response to treatment and corresponding disease remission status. This TBNG landscape establishes its utility as a novel biomarker for HM diagnosis, subtyping, risk stratification, treatment response, and MRD monitoring.

Cytoskeletal remodeling and mitochondrial bioenergetics play important roles in thrombocytopoiesis and platelet function. Recently, α-actinin-1 mutations have been reported in patients with congenital macrothrombocytopenia. However, the role and underlying mechanism of α-actinin-1 in thrombocytopoiesis and platelet function remain elusive. Using MK-specific α-actinin-1 knockout (PF4-Actn1-/-) mice, we demonstrated that PF4-Actn1-/- mice exhibited reduced platelet counts. The decreased platelet number in PF4-Actn1-/- mice was due to defects in thrombocytopoiesis. H&E staining and flow cytometry revealed a decrease in the number of MKs in the bone marrow of PF4-Actn1-/- mice. The absence of α-actinin-1 increased the proportion of 2 N-4 N MKs and decreased the proportion of 8 N-32 N MKs. CFU-MK colony formation, the ratio of proplatelet formation-bearing MKs, and MK migration in response to SDF-1 signaling were inhibited in PF4-Actn1-/- mice. Platelet spreading, clot retraction, aggregation, integrin αIIbβ3 activation, and P-selectin exposure in response to various agonists were decreased in PF4-Actn1-/- platelets. Notably, PF4-Actn1-/- platelets inhibited calcium mobilization, ROS generation, and actin polymerization in response to collagen and thrombin. Furthermore, the PF4-Actn1-/- mice exhibited impaired hemostasis and thrombosis. Mechanistically, proteomic analysis of low-ploidy (2-4 N) and high-ploidy (≥8 N) PF4-Actn1-/- MKs revealed that α-actinin-1 deletion reduced platelet activation and mitochondrial function. PF4-Actn1-/- platelets and Actn1 KO 293T cells exhibited reduced mitochondrial membrane potential, mitoROS generation, mitochondrial calcium mobilization, and mitochondrial bioenergetics. Overall, in this study, we report that mice with α-actinin-1 deficiency in MKs exhibit low platelet count and impaired platelet function, thrombosis, and mitochondrial bioenergetics.

Paxillin and kindlin are essential regulatory proteins involved in cell adhesion, migration, and signal transduction. Paxillin influences cytoskeletal dynamics by interacting with multiple signaling proteins, while kindlin regulates integrin activation, affecting adhesion and motility. This review examines the structures and functions of these proteins, focusing on their roles in cancer progression, immune response, and therapeutic potential. The cooperation between paxillin and kindlin in integrin activation and focal adhesion dynamics offers valuable insights into tumor metastasis, immune function, and tissue repair.

The pandemic of coronavirus disease 2019(COVID-19)has impacted our lifestyles.On the one hand,the patients with hematological malignancies(HM)are more vulnerable to COVID-19 infection.Once infected with COVID-19,these patients tend to develop into severe type with a higher mortality rate.Although patients with HM demonstrated a reduced response to COVID-19 vaccines,they still can benefit from vaccine injection with reduced rates of viral infection and incidence of severe cases.The combination of monoclonal antibodies and antiviral drugs is helpful to the COVID-19 treatment of patients with HM.On the other hand,COVID-19 infection can lead to a delay of hematopoietic recovery and low immunity in patients with HM.For HM patients with COVID-19 infection,to reduce the intensity and shorten the course of radiotherapy and chemotherapy is needed.This article will review the interaction between COVID-19 infection and HM.

Myeloproliferative neoplasms (MPNs) encompass three principal subtypes: polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). These hematologic malignancies originate from clonal hematopoietic stem cells (HSCs) and exhibit pathological overproduction of myeloid lineage cells. Recent advances in molecular diagnostics, particularly the precise detection of core driver mutations (JAK2 V617F, CALR, and MPL) and non-driver mutations (ASXL1, TET2, SRSF2), has refined diagnostic precision and risk stratification. A variety of prognostic models for MPNs provide guidance for treatment. Treatment methods mainly include bloodletting therapy, low-dose aspirin anticoagulant therapy, cytoreductive therapy, and allogeneic hematopoietic stem cell transplantation (HSCT). JAK inhibitors (such as ruxolitinib) remain the basic therapeutic drugs. However, emerging strategies targeting epigenetic dysregulation and the interaction in the immune microenvironment (such as interferon-α) show promise in reducing drug resistance. New methods, including combination therapy (combination of JAK inhibitors and BCL-XL inhibitors) and mutation-independent immunotherapy, are under investigation. This review summarizes the latest advancements in the diagnosis and treatment of MPNs, highlighting the importance of molecular mechanisms in guiding therapeutic approaches and the potential for precision medicine in the future.

Lymphoma-associated hemophagocytic lymphohistiocytosis (LA-HLH) is a life-threatening hyperinflammatory syndrome, and hierarchical management based on a prognostic model is important. The endothelial activation and stress index (EASIX) score has demonstrated prognostic utility in recipients of allogeneic stem cell transplantation and chimeric antigen receptor (CAR) T-cell therapy. However, its role in LA-HLH remains unestablished. We conducted a multicenter retrospective analysis of patients with LA-HLH from 28 medical centers to explore the prognostic impacts of EASIX in LA-HLH. EASIX was calculated using baseline lactate dehydrogenase, serum creatinine, and platelet counts. A total of 490 patients with LA-HLH were included and stratified by EASIX quartiles (Q1-Q4). Patients with a higher EASIX score had significantly inferior 2-month survival and overall survival, according to the Kaplan-Meier analysis (log-rank p < 0.001). In multivariable analyses, after adjustment for age, gender, lymphoma type, splenomegaly, bone marrow infiltration, lymphoma status (treatment-naïve versus relapsed/refractory), hemoglobin, absolute neutrophil count, serum ferritin levels, and aspartate aminotransferase, the highest EASIX quartile (Q4) exhibited a 7.01-fold risk of death compared to the lowest quartile (Q1) (Hazard ratio [HR] = 7.01, 95% confidence interval [CI]: 3.98-12.36; p < 0.001). Additionally, the restricted cubic splines (RCS) analysis illustrated an increase in the risk of mortality with an increasing EASIX score. Our findings support EASIX being a robust, universally accessible prognostic marker for LA-HLH, strongly associated with early mortality risk. This index can be used to stratify the risk levels of patients with LA-HLH and predict their survival outcomes.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a revolutionary approach in the treatment of hematological malignancies, including acute lymphoblastic leukemia, B-cell lymphoma, and multiple myeloma. Despite its promise, the clinical efficacy is often hampered by transient efficacy and subsequent relapse, which curtail the long-term success of this treatment. Current research focuses on overcoming these obstacles by exploring multitarget strategies and optimizing CAR-T cell design. This review summarizes recent insights into the resistance mechanisms associated with CAR-T cell therapy, and delineates emerging strategies for optimized CAR construction, including targeting multiple antigens, improving CAR design, and enhancing T-cell persistence. The goal is to provide a comprehensive overview of the field’s current landscape to guide future research and the clinical application of CAR-T cell therapies.

Objective It has been documented that D-dimer levels have potential utility as a measure of tumor activity in diffuse large B-cell lymphoma (DLBCL), however whether it can be used as a predictive marker of treatment outcome has not been established. This study means to retrospectively evaluate the role of D-dimer in prediction of treatment efficacy in patients with DLBCL. Materials and methods 151 patients with newly diagnosed DLBCL were enrolled. Blood samples were taken from those patients during the initial visit to our hospital and again after two cycles of chemotherapy to measure D-dimer levels. The link between plasma D-dimer concentrations and patients' clinical characteristics was explored before and after treatment. Results Patients showed statistically different plasma D-dimer levels at initial consultation across the four treatment-response groups [ complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD)]. Those in CR group had significantly lower D-dimer levels at initial consultation than those in PR and PD groups (p < 0.05). After chemotherapy, the PR group had considerably lower D-dimers than the SD and PD groups did (p < 0.05). The D-dimer difference percentage was lower in PR group than that in PD group (p < 0.05). Conclusion Patients who respond well to chemotherapy typically exhibit lower D-dimer levels at the initial diagnosis. Those in the SD or PD groups usually experience a greater increase in D-dimer levels following chemotherapy. Consequently, variations in plasma D-dimer levels before and after treatment may offer valuable insights for evaluating the efficacy of chemotherapy treatment.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and fatal disease with a low survival rate. It is important to identify the patients at risk of poor prognosis among HLH patients. In this multicenter and retrospective study, we reviewed 90 newly diagnosed HLH patients treated at the Second Affiliated Hospital of Nanjing Medical University and the First Affiliated Hospital of Anhui Medical University from April 2014 to February 2025. Four pre-treatment clinical characteristics of HLH patients were confirmed to be the independent risk factors: age (hazard ratio (HR) 1.041, 95% confidence interval (CI)1.023-1.059, p < 0.001); splenomegaly (HR 2.112, 95% CI 1.178-3.787, p = 0.012); platelet (PLT) count (HR 0.992, 95% CI 0.984-0.999, p = 0.035); aspartate aminotransferase (AST) (HR 1.002, 95% CI 1.001-1.003, p < 0.001). Subsequently, the patients' prognostic risk scores were calculated based on these four risk factors to stratify patients to high-risk and low-risk groups. Besides, these four factors were included in the final clinical prediction model. Receiver operating characteristic (ROC) curves revealed that this model had a good discrimination with optimism-corrected area under the curve (AUC) values of 0.78 (95% CI: 0.68-0.88) for 30-day mortality and 0.82 (95% CI: 0.74-0.92) for 90-day mortality. The calibration curves aligned with the model predictions and actual observations. The decision curve analysis also confirmed our model's robust predictive power. These results point out that age, splenomegaly, PLT, and AST levels are independent indicators of overall survival in patients with HLH and that the proposed model has a good prognostic value.

This study aimed to examine variations in iron deposition, neuromelanin (NM) content, gamma-aminobutyric acid (GABA) and glutamate-glutamine complex (Glx) levels within the nigrostriatal pathway in early-stage Parkinson’s disease (PD) patients with and without Rapid Eye Movement Sleep Behavior Disorder (RBD). Twenty-two early-stage PD patients with RBD (PD-RBD), 33 without RBD (PD-nRBD), and 36 healthy controls (HC) were prospectively recruited and underwent 3 T MRI and 1H-MRS scans. GABA levels in the left basal ganglia were elevated in PD-nRBD versus HC (P = 0.014), whereas they were decreased in the PD-RBD relative to the PD-nRBD (P = 0.018). Iron deposition and NM content in the bilateral substantia nigra (SN) showed no differences between PD subgroups. Despite similar SN iron and NM content, the GABAergic system alteration provides novel insights into the pathophysiology of RBD in PD.

Aims Dedicator of cytokinesis 2 (DOCK2), a member of the DOCK family of guanine nucleotide exchange factors that specifically act on the Rho GTPases including Rac and Cdc42, plays pivotal roles in the regulation of leukocyte homeostasis. However, its functions in platelets remain unknown.Methods and results Using mice with genetic deficiency of DOCK2 (Dock2-/-), we showed that Dock2-/- mice exhibited a macrothrombocytopenic phenotype characterized as decreased platelet count and enlarged platelet size by transmission electron microscopy. Dock2-/- megakaryocytes had reduced polyploidization determined by propidium iodide staining and defective proplatelet formation by confocal microscopy. DOCK2 deficiency led to enriched F-actin level in resting platelets but defective F-actin assembly in activated platelets by phalloidin staining, and mechanistically, attenuated activity of Rac1, unchanged Cdc42 but enhanced RhoA measured by immunoprecipitation of GTP-bound proteins. Immunoblotting analysis showed that Dock2-/- platelets had reduced immunoreceptor tyrosine-based activation motif signaling downstream of impaired clustering of GPVI receptors determined by stochastic optical reconstruction microscopy. Further, DOCK2 deficiency resulted in reduced density and branches of fibrin fibres in the clots in vitro and diminished platelet aggregation in a microfluidic chamber ex vivo. Dock2-/- platelets exhibited impaired incorporation into a growing thrombus in cremaster arterioles following allogeneic transfusion into a WT recipient and defective heterotypic interactions with neutrophils in cremaster venules as reflected by decreased platelet-neutrophil aggregate formation in vitro under stirring condition. In addition, myeloid deficiency of DOCK2 caused prolonged tail bleeding times. Finally, pharmacological inhibition of DOCK2 using a small-molecular inhibitor CPYPP suppressed actin dynamics leading to impaired responses to GPVI activation and defects in platelet spreading, clot retraction, and thrombus formation.Conclusion DOCK2 plays critical roles in the regulation of platelet biogenesis and functions by controlling Rac1 activity and cytoskeletal actin dynamics and may be a novel target for the treatment of thrombotic and thrombo-inflammatory diseases.

Acquired pure red cell aplasia (PRCA) is anemia associated with the absence of erythroblasts and is characterized by persistent and easy recurrence. However, the underlying mechanisms of acquired PRCA remain obscure, and the role of gene mutations in the pathogenesis of acquired PRCA is not fully characterized. In the present study, we detected thirty newly diagnosed patients with acquired PRCA using whole exome sequencing, and a potential role for STK10 in acquired PRCA was uncovered. The mRNA levels of STK10 in three patients with STK10 mutations were decreased. These three patients had a poor response to immunosuppressive therapy and two died in the follow-up period. Here we report that knockdown of STK10 inhibits erythroid differentiation and promotes apoptosis of K562 cells. We show that knockdown of STK10 resulted in inhibition of ribosome biogenesis and reduced ribosome levels in K562 cells. We also show that the p53 signaling pathway is activated by knockdown of STK10. Our results imply that ribosome biogenesis downregulation together with pathological p53 activation prevents normal erythropoiesis. Our study uncovers a new pathophysiological mechanism leading to acquired PRCA driven by STK10 mutations.

Chimeric antigen receptor(CAR)T cell therapy,one of the most promising tumor treatments,combines the targeted recognition of antigen and antibody with the killing effect of T cells.CAR-T has shown a strong therapeutic effect in lymphoid tumors and been applied in clinical practice.However,in the treatment of acute myeloid leukemia(AML),no effective and specific target like CD 19 in lymphoid tumors has been found.Therefore,the key research direction is to try multiple probabilities and use optimization strategies to enhance efficacy and reduce toxicity.This review introduces the latest research progress of AML targets in CAR-T therapy in recent years,analyzes the related problems that need to be solved at present,and summarizes the optimization construction strategies mentioned in the research.Hope it can provide reference for related research and clinical application of related product.

Corona virus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has affected the whole world. Acquired thrombotic thrombocytopenic purpura (TTP) has been reported after administration of mRNA- or adenoviral vector-based COVID-19 vaccines, including Ad26.COV2-S, BNT162b2, mRNA-1273, and ChAdOx1 nCov-19. However, whether inactivated vaccines, such as CoronaVac, could cause TTP and whether the symptoms in TTPs caused by inactivated vaccines are different from previously reported cases are unknown. In this study, two cases were reported. Both cases developed TTP after the second CoronaVac vaccination shot, but not the first. They demonstrated symptoms of fever, neurological abnormalities, renal dysfunction, thrombocytopenia, and hemolysis. Both patients achieved complete remission through several sessions of plasma exchanges and immune suppression. The incidence of TTP in Nanjing area was analyzed. The number of patients with TTP was 12 in 2019, 6 in 2020, 16 in 2021, and 19 in 2022. To the authors’ knowledge, this report is the first report of TTP associated with inactivated COVID-19 vaccine (CoronaVac). The rarity and delayed onset may be due to the relatively milder immune response caused by the inactivated vaccines than mRNA-based ones. Timely plasma exchange is a vital treatment for CoronaVac-related TTP, similar to activated vaccine-related TTP.