中国实验血液学杂志最新文献

Objective: To analyze the multi antigen distribution characteristics of Rh blood group system in Shunde area of Guangdong Province, explore the feasibility of Rh phenotype compatible blood transfusion for blood recipients in this area, and formulate the precise blood transfusion strategies.

Methods: From June 2022 to December 2024, 113 226 hospitalized patients scheduled for blood transfusion in Shunde Hospital of Southern Medical University and 30 832 blood donors' blood samples provided by Shunde central blood station in the same period were detected for ABO blood group and Rh phenotype by microcolumn gel method, and the Rh phenotype data of the recipients and blood donors were compared and analyzed.

Results: Among 113 226 blood samples, 112 963 cases (99.77%) were RhD positive, with CCDee (54.96%) and CcDEe (28.21%) phenotypes being the main phenotypes; 263 cases (0.23%) were RhD negative, with ccDee (50.19%) and CcDee (36.88%) as the main phenotype. Among 30 832 blood donor samples, CCDee (54.65%) and CcDEe (27.93%) were the main phenotypes of Rh phenotype with RhD positive. The positive rates of D, C, c, E and e antigens of blood recipients and blood donors were in the same order from high to low D>e>C>c>E. The frequency of e antigen in RhD positive recipients with different ABO blood groups was statistically different from that of blood donors (P <0.05), while there was no statistical difference in the other four antigens (P >0.05), the distribution of ccDEe phenotypes was statistically different (P <0.05), but there was no statistical difference in the distribution of other eight phenotypes (P >0.05). In RhD positive recipients, the probability of finding compatible blood for phenotype CcDEe was 100%, the probability of finding compatible blood for phenotype CCDee, CCDEe and DcDee was 54%-65%, and the probability of finding compatible blood for other phenotypes was less than 10%. Providing blood with CCDee and ccDEE phenotypes according to Rh blood matching scheme can meet the needs of more than 99% of patients with 9 Rh phenotype compatible blood transfusion in this region.

Conclusion: Rh phenotype detection should be carried out for hospitalized patients to be transfused, and the precise transfusion strategy of Rh phenotype isotype or compatibility should be implemented to make the transfusion treatment of patients more safe and reliable.

Objective: To investigate the association between genetic variation sites and blood group phenotypes in a family with the ABw subtype.

Methods: A 22-year-old male proband and six family members who underwent health examinations at the Department of Transfusion Medicine, 960th Hospital of the PLA Joint Logistics Support Force on April 8, 2023 were enrolled. ABO blood group phenotyping of the proband and family members was performed using the tube method. Direct sequencing of PCR products covering the ABO gene promoter region, intron 1, and exons 1-7 was conducted for the proband and family members. Clonal sequencing of exons 6 and 7 was performed for the proband.

Results: The serological phenotype of the proband was identified as ABw. Direct sequencing of PCR products revealed that the proband's ABO gene promoter region contained two variants (c.-105G>C and c.-106G>C), intron 1 contained the variant c.28+5708G>A, and exon 6 contained the variant c.255C>T. Blood group genotype of the proband was ABO*A1.02/ABO*B with the c.255C>T variant. Family analysis showed that the proband's mother, brother, elder niece, and younger niece also carried the c.255C>T variant in exon 6. The proband's mother had variants c.-105G>C and c.-106G>C in the promoter region, c.28+6127T>C and c.28+6154A>G in the intron region, with a genotype of ABO*O.01.01/ABO*B and the c.255C>T variant. The proband's brother, elder niece, and younger niece exhibited no promoter region abnormalities but carried variants c.28+6272C>T, c.28+6173A>G, c.28+6284T>C, and c.28+6297A>T in intron 1. The brother's genotype was ABO*A1.02/ABO*B with c.255C>T, the elder niece's genotype was ABO*B.01/ABO*B with c.255C>T, and the younger niece's genotype was ABO* O.01.01/ABO*B with c.255C>T. The proband's father had a genotype of ABO*A1.02/ABO*A1.02, and the sister-in-law's genotype was ABO*O.01.01/ABO*B.01 .

Conclusion: The c.255C>T variant in exon 6 of the ABO blood group B allele (α-1,3-galactosyltransferase gene) exhibits hereditary characteristics and exerts a negative regulatory effect on glycosyltransferase activity to a certain extent.

Chimeric antigen receptor (CAR) T cell therapy has made a major breakthrough in the treatment of hematological malignancies. However, more and more studies have shown that factors such as T-cell exhaustion, tumor antigen modulation, immunosuppressive tumor microenvironment, and CAR-T cell dysfunction can lead to relapse and CAR-T cell resistence in hematologic malignancies. Developing dual-targeted CAR-T cells, exploring new immune targets, blocking CAR-T cell exhaustion, combining CAR-T cells with other therapies, implementing bridging therapies, and designing novel immunotherapies may be strategies to address CAR-T cell resistance. This article reviews the mechanisms of resistance to CAR-T cell therapy in hematological malignancies and the corresponding coping strategies.

Objective: To investigate the molecular characteristics of low-risk acute myeloid leukemia (AML) at recurrence, and analyze the factors affecting retreatment efficacy and prognosis.

Methods: A retrospective analysis was conducted on the clinical and laboratory data of 31 patients with newly diagnosed low-risk AML who relapsed during consolidation treatment or follow-up after treatment in our hospital from April 2017 to January 2023. Gene mutations before and after relapse were compared, retreatment efficacy following relapse was evaluated, and univariate and multivariate analyses were performed to identify factors influencing treatment efficacy and prognosis.

Results: Gene sequencing results after relapse showed that the most common newly acquired mutation was FLT3-ITD , while RAS mutation detected at initial diagnosis were predisposed to loss of expression during relapse. The median overall survival (OS) after relapse for the entire cohort was 349 (170-528) days, with non-hematopoietic stem cell transplantation (HSCT) group and HSCT group demonstrating median survival times of 210 (106-314) days and not reached, respectively (P =0.001). Multivariate analysis revealed that age ≥60 years was a significant risk factor for achieving remission after retreatment in initially diagnosed low-risk AML patients who experienced relapse (OR =18.222, 95%CI : 1.188-279.597, P =0.037). Additionally, DNMT3A mutation was identified as an independent risk factor for OS (HR=13.165, 95%CI : 2.018-85.877, P =0.007), while HSCT post-relapse demonstrated significant survival benefits (HR=0.133, 95%CI : 0.025-0.698, P =0.017) and served as an independent protective factor for OS.

Conclusion: Relapsed low-risk AML is often associated with loss of RAS and novel mutations in FLT3-ITD . Age ≥60 years and DNMT3A mutations were identified as independent adverse factors for achieving subsequent remission and post-relapse survival, respectively, while HSCT significantly improved patient outcomes.

Objective: To investigate the effect of COX6C on the proliferation of multiple myeloma (MM) cells and its mechanism of action.

Methods: The expression of COX6C in MM cell lines were detected by RT-PCR. siRNA technology was used to knockdown COX6C expression in OPM2 cells. MTT assay and flow cytometry were employed to assess the effect of COX6C knockdown by siRNA on cell proliferation, mitochondrial membrane potential (ΔΨm), and intracellular adenosine triphosphate (ATP) levels. The mitochondrial morphological changes in OPM2 cells pre- and post- siRNA-mediated COX6C knockdown were observed by transmission electron microscopy (TEM).

Results: The relative expression level of COX6C was significantly increased in MM cell lines (P <0.01). Following siRNA-mediated COX6C knockdown, OPM2 cell proliferation was inhibited, with viable cells accounting for 62.32%±3.43% and 47.01%±5.12% after 48 and 72 hours of culture, respectively. siRNA-mediated COX6C knockdown also caused significant reductions in mitochondrial membrane potential and intracellular ATP levels (P <0.05), accompanied by mitochondrial shortening, swelling, and incomplete cristae structures.

Conclusion: COX6C may promote the proliferation of MM cells by altering the mitochondrial structure and elevating intracellular ATP levels.

Objective: To analyze the potential risk factors for early relapse/progression in patients with multiple myeloma (MM) and develop a risk prediction model based on these factors.

Methods: A retrospective analysis was conducted on 187 newly diagnosed multiple myeloma (NDMM) patients who treated at the Affiliated Hospital of North Sichuan Medical College from February 2014 to December 2020. The clinical, laboratory examination, and follow-up data of patients experiencing relapse/progression within 24 months after treatment (ER/EP24) were analyzed using univariate and multivariate analyses, and a nomogram prediction model was established.

Results: Among the 187 patients, 58 (31.0%) experienced ER/EP24, with a median survival time of only 24 months. The results of multivariate logistic regression analysis showed that failure to achieve partial response (PR) or better after 3-4 cycles of chemotherapy and albumin (ALB) levels <35 g/L were independent risk factors for ER/EP24 (P < 0.05). These factors, along with other clinically relevant variables, were further incorporated into the nomogram prediction model. The model demonstrated a concordance index (C-index) of 0.784, indicating strong predictive accuracy.

Conclusion: MM patients experiencing ER/EP24 exhibit poor outcome, and the nomogram model developed in this study effectively predicts the risk of ER/EP24 in NDMM patients, providing a valuable tool for clinical risk assessment.

Objective: To investigate the incidence, clinical characteristics, and complications of Torque teno virus (TTV) in children after hematopoietic stem cell transplantation (HSCT).

Methods: A total of 40 children with hematological diseases who underwent HSCT were selected, and metagenomic next-generation sequencing (mNGS) technology was used to detect the gene sequences of pathogenic microorganisms in the blood. Combined with clinical data, the characteristics of TTV infection were analyzed.

Results: Among the 40 pediatric patients post-HSCT, the TTV positive rate was 42.5% (17/40). There were no statistically significant differences between the TTV-positive group and the TTV-negative group in sex, age, white blood cell count(WBC), red blood cell count(RBC), hemoglobin, platelet count, neutrophil count, lymphocyte count, and high-sensitivity C-reactive protein (all P >0.05). The incidence of TTV infection was significantly higher in children who underwent haploidentical HSCT and in those with bone marrow stem cells (BMSC) as the transplant source (P <0.05). However, there were no significant differences in the TTV infection rate among patients with different disease types, different HLA matching statuses, or different engraftment times of neutrophils and platelets (all P >0.05). Among 17 children infected with TTV, 13(76.5%) had co-infections with other viruses, mainly including cytomegalovirus (58.8%, 10/17), human polyomavirus (41.2%, 7/17), and Epstein-Barr virus (17.6%, 3/17). In children with TTV infection, the most common complications were sepsis (82.4%), graft-versus-host disease (GVHD) (70.6%), pulmonary infection (41.2%), and hemorrhagic cystitis (17.6%). The incidence of GVHD in the TTV-positive group was significantly higher than that in the TTV-negative group (P <0.05).

Conclusion: TTV infection is common in children undergoing HSCT, and it is prone to be complicated with cytomegalovirus infection and GVHD, which has an important influence on the clinical outcomes.

Objective: To construct a simple score scale for donation-related vasovagal reaction (DRVR) based on Logistic regression model and evaluate its application value.

Methods: A retrospective study was conducted on 5000 blood donors from Zhangjiakou Central Blood Station from January 2018 to January 2023. The baseline data of the blood donors were collected. Logistic regression analysis was performed on them to construct a DRVR prediction model. A DRVR simple score scale was built based on the odds ratios. The score intervals were divided into low-risk, medium risk, and high-risk categories, the application value of the scale was evaluated based on the prediction efficacy of Logistic regression model.

Results: The incidence of DRVR among the blood donors was 4.12%. The Logistic regression model identified eight independent risk factors for DRVR, including advanced age, female gender, low body mass index, first blood donation, hypotension, low hemoglobin level, long blood collection time, and high blood donation volume (all P < 0.05). A simple DRVR score scale was constructed based on the odds ratio values. The scale scores were divided into three intervals: low-risk (total score <6), moderate risk (total score 6-11), and high-risk (total score >11,≤17). The area under the curve(AUC) for predicting DRVR in low-risk, medium risk, and high-risk blood donors based on Logistic regression model were 0.784 (95% CI : 0.742-0.844), 0.806 (95% CI : 0.752-0.883), and 0.842 (95% CI : 0.761-0.925), respectively. The consistency indices were 0.794 (95% CI : 0.705-0.828), 0.800 (95% CI : 0.745-0.852), and 0.839 (95% CI : 0.782-0.917), respectively. The calibration curves did not deviate from the ideal fit. The results of external validation showed that the receiver operating characteristic curve fittings were relatively ideal (all P >0.05), and there were no statistically significant difference in AUC (all P >0.05).

Conclusion: The DRVR simple score scale has a relatively ideal ability to distinguish the blood donors and can provide some reference for quickly narrowing the scope of high-risk groups. DRVR simple score scale has certain application value, but still needs to be continuously improved and optimized.

Objective: To explore the difference of type 2 innate lymphoid cell (ILC2), IL-9 and related cytokines between chronic lymphocytic leukemia (CLL) patients and normal individuals, as well as the correlation between ILC2 and IL-9 and other cytokines in CLL patients.

Methods: Flow cytometry was used to detect the expression of ILC2 and regulatory T cells (Tregs) in peripheral blood of 26 CLL patients at initial diagnosis and 10 healthy controls. RT-qPCR was used to detected IFN-γ, TGF-β, IL-9 and IL-10 mRNA in peripheral blood mononuclear cell (PBMC). ELISA was used to detect serum IFN-γ, TNF-α, TGF-β, IL-9, IL-10 and IL-21. ILC2 and IL-9 were observed in the cervical lymph node of 12 CLL patients at initial diagnosis and 12 patients with reactive lymphoid hyperplasias by multiplex indirect immunofluorescence staining. Spearman test was used to analyze the correlation between peripheral blood ILC2 and IL-9, IL-9 and IL-21, IFN-γ mRNA and IL-10 mRNA in CLL patients. Pearson test was used to analyze the correlation between TNF-α and TGF-β in CLL patients.

Results: Compared with control group, the proportions of ILC2 and Tregs were significantly increased in CLL group (both P < 0.05). The mRNA expressions of IFN-γ, IL-9, IL-10 and TGF-β in PBMCs of CLL patients were significantly increased (all P < 0.05). In CLL patients, the expressions of IFN-γ, TNF-α, TGF-β, IL-9 and IL-10 in serum were significantly increased (all P < 0.01), while IL-21 slightly increased without statistical difference (P >0.05). In CLL patients, the peripheral blood ILC2 was positively related to IL-9 (r =0.56), IL-9 was positively related to IL-21 (r =0.397), IFN-γ mRNA was positively related to IL-10 mRNA (r =0.623), and TNF-α was positively related to TGF-β (r =0.577). Compared with reactive lymphoid hyperplasias patients, the mean fluorescence intensities of GATA3 and CRTH2 representing ILC2 and IL-9 in cervical lymph nodes were significantly increased in the CLL group (all P < 0.001), and showed colocalization.

Conclusion: In CLL patients, the proportions of ILC2 and IL-9 in peripheral blood and lymph nodes increase, and ILC2 and IL-9 show colocalization in lymph nodes. There is a positive correlation between ILC2 and IL-9 in the peripheral blood of CLL patients, the ability of ILC2 to secrete IL-9 is increased, and ILC2 may affect the occurrence and development of CLL through IL-9.

Triple-negative myeloproliferative neoplasms (TN-MPN) are diseases characterized by absence of the three driver mutations in JAK2, CALR, or MPL, but still exhibit histological and phenotypic features sufficient to diagnose myeloproliferative neoplasms (MPN). Approximately 10% to 20% of essential thrombocythemia (ET) and 5% to 10% of primary myelofibrosis (PMF) cases are reported to be triple negative. TN-MPN may carry non-classical driver mutations at JAK2 or MPL, or other gene mutations, including somatic mutations of chromatin structure, epigenetic modifiers (TET2, IDH1/2), splicing factors (SF3B1, SRSF2, U2AF1, ZRSR2), and cytokine signaling regulators (CBL, SH2B3), etc., and there is evidence of clonal hematopoiesis. This article reviews the latest research progress in the pathogenesis, diagnosis, clinical features, prognosis and treatment of TN-MPN.