中国实验血液学杂志最新文献

Patients with myeloproliferative neoplasms (MPNs) are at risk of developing solid tumors. Although the connection between MPN and solid tumors has been widely discussed, the cause remains to be explored. Some studies show that the MPN is considered to trigger a second cancer, but others suggest both diseases seem to share the same origin. In recent years, more and more studies have found that genetic susceptibility, drugs, chronic inflammation, immune function abnormalities and clonal hematopoiesis of indeterminate potential are related to the development of second cancers. In this review, we try to summarize the new advances of biological characteristics and pathogenesis of second cancers in MPNs.

There is a complex biological mechanism in the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (PKB/Akt)/mammalian target of rapamycin (mTOR) signaling pathway, which plays a key role in the development and development of lymphoma. In this review, the relevant literature of PI3K inhibitor research in the past five years summarized and analyzed, and found that the research and development, application, efficacy, and adverse reactions of PI3K inhibitors are the current research hotspots, and the positive results of PI3K inhibitors in clinical trials and basic research have strongly demonstrated the potential of PI3K inhibitors in personalized treatment of lymphoma. In order to maximize the clinical benefits, a variety of strategies need to be explored, including novel drugs with better selectivity and safety, and related combination therapies.

Objective: To detect the serum levels of 25(OH)D, miR-125b-5p, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGFA) in patients with multiple myeloma (MM), and explore the role of miR-125b-5p/HIF-1α pathway in the involvement of vitamin D deficiency in the pathogenesis of MM.

Methods: Fifty three newly diagnosed/relapsed MM patients admitted to the department of hematology of our hospital from October 2021 to December 2023 were included. Meanwhile, 25 healthy individuals matched in gender and age from our hospital's Health Management Center were selected as controls. The serum level of 25(OH)D was monitored by mass spectrometry, the serum level of miR-125b-5p was detected by real-time fluorescence quantitative PCR, and serum levels of HIF-1α and VEGFA were measured by enzyme-linked immunosorbent assay. The levels of 25(OH)D, miR-125b-5p, HIF-1α, and VEGFA were compared between the two groups. According to the level of 25(OH)D, the MM patients were divided into vitamin D deficiency group (< 20 ng/ml) and vitamin D non-deficiency group (≥20 ng/ml), and the levels of miR-125b-5p, HIF-1α, and VEGFA were compared between the two groups. The correlations between 25(OH)D, miR-125b-5p, HIF-1α and VEGFA were analyzed. The receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of 25(OH)D combined with miR-125b-5p for newly diagnosed MM.

Results: The level of 25(OH)D in MM patients was significantly lower than that in control group (P < 0.01). There was no significant difference in 25(OH)D level between newly diagnosed and relapsed MM patients (P >0.05). Compared with the control group, the level of miR-125b-5p was significantly reduced in MM patients (P < 0.01), while the levels of HIF-1α and VEGFA were significantly increased (both P < 0.001). In MM patients, the miR-125b-5p level in the vitamin D deficiency group was significantly decreased than that in the non-deficiency group (P < 0.01), while the levels of HIF-1α and VEGFA were significantly increased (both P < 0.05). In MM patients, 25(OH)D was positively correlated with miR-125b-5p, while negatively correlated with HIF-1α and VEGFA (both P < 0.05). Moreover, miR-125b-5p was negatively correlated with HIF-1α and VEGFA (both P < 0.05). The area under the curve (AUC) for diagnosing MM with 25(OH)D, miR-125b-5p, and their combination were 0.699, 0.751, and 0.791, respectively.

Conclusion: The incidence of vitamin D deficiency is high in MM patients. Vitamin D deficiency may promote angiogenesis and participate in the occurrence and development of MM by downregulating miR-125b-5p and upregulating HIF-1α and VEGFA expression.

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 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.