中国实验血液学杂志最新文献

Objective: To investigate the effect of platelet irradiation on the efficacy and safety of platelet transfusion in children with hematological disorders.

Methods: The platelet transfusion of 56 pediatric patients in the Hematology Department of Wuhan Children's Hospital from January to December 2023 were retrospective analyzed. According to whether the platelets transfused by the patient have been irradiated, they are divided into irradiation group and non irradiation group. The effect of platelet irradiation on efficacy rate of transfusion and incidence of transfusion adverse reactions was analyzed.

Results: Fifty-six patients with hematological disorders received 608 platelet transfusions, with 83 transfusions ineffective and an inefficiency rate of 13.65%. Twenty-nine times of adverse transfusion reactions occurred, with a transfusion reaction incidence rate of 4.77%. The 24-hour CCI value of the irradiation group was lower than that of the non irradiation group ( Z=4.120, P < 0.01), and the effective rate of transfusion in the irradiation group was lower than that in the non irradiation group (χ²=8.595, P <0.01). The incidence of adverse reactions during transfusion in the irradiation group was lower than that in the non irradiation group (χ²=4.153, P <0.05). In children with acute leukemia, there were statistical differences in 24 h CCI, the effective rate of transfusion, and adverse transfusion reactions between the irradiation and non-irradiation groups.

Conclusion: Platelet irradiation can reduce the effective rate of platelet transfusion in children with hematological disorders, but can reduce the incidence of adverse transfusion reactions. To ensure the safety of blood use for pediatric patients, it is recommended to transfuse irradiated platelets to individuals who are susceptible to transfusion associated graft-versus-host disease (TA-GVHD), especially children with acute leukemia.

Objective: To investigate the clinical characteristics of patients with multiple myeloma (MM) complicated by bone lesions and the risk factors associated with bone lesions.

Methods: The clinical data of 294 newly diagnosed MM patients in Gansu Provincial Hospital from January 2017 to June 2021 were retrospectively analyzed. The patients were divided into the bone lesion group (154 cases) and the non-bone lesions group (140 cases) based on the presence of absence of bone lesions at diagnosis. The general data and laboratory parameters were compared between the two groups. The risk factors for bone lesions in MM patients were analyzed by logistic regression analysis, and the characteristic (ROC) curves were plotted to assess the predictive value of each risk factor for the occurrence of bone lesions in MM patients.

Results: Compared to the non-bone lesion group, the bone lesion group had significantly higher serum calcium levels and significantly greater proportions of patients with Durie-Salmon (DS) stage III, and bone pain (all P < 0.05). Logistic regression analysis showed that elevated serum calcium (OR =5.135, 95%CI : 1.931-13.653, P =0.001), DS stage III (OR =1.841, 95%CI : 1.019-3.328, P =0.043), and bone pain (OR=8.208, 95%CI : 4.761-14.151, P < 0.001) were independent risk factors for bone lesions in MM patients. ROC curve analysis showed that serum calcium (AUC=0.619, 95%CI : 0.555-0.683, P < 0.001) and bone pain (AUC=0.743, 95%CI : 0.692-0.793, P < 0.001) had predictive value for bone lesions in MM patients.

Conclusion: MM patients have a high incidence of bone lesions, and active monitoring and management of risk factors may improve treatment outcomes and prognosis.

Objective: To study the mechanism of arsenic trioxide (ATO) combined with metformin (MET) in promoting apoptosis of leukemia cells.

Methods: CCK-8 method was used to detect the viability of leukemia cell line KG1a, K562, and THP1 cells treated by ATO monotherapy, MET monotherapy, and ATO combined with MET. Flow cytometry was used to detect cell cycle and apoptosis. RT-qPCR was used to detect the mRNA expression of PI3K/Akt and LKB1/AMPK pathway-related genes. Western blot was used to detect the expression of PI3K/Akt and LKB1/AMPK pathway-related proteins and autophagy-related protein LC3B and P62.

Results: Compared with the ATO monotherapy group, ATO combined with MET significantly inhibited the growth of KG1a, K562 and THP1 cells, and the difference in KG1a cells was more statistically significant. The combination of the two drugs induced KG1a cell cycle arrest, promoted apoptosis, increased the expression of autophagy-related protein LC3B and P62, up-regulated the mRNA expression levels of PI3K/Akt pathway and LKB1/AMPK pathway-related genes, as well as the expression of LKB1/AMPK pathway-related proteins, and down-regulated the expression of PI3K/Akt pathway-related proteins.

Conclusion: ATO combined with MET promotes apoptosis by up-regulating LKB1/AMPK and down-regulating PI3K/Akt signaling pathway to regulate the autophagy of leukemia cells.

Objective: To explore the feasibility of modifying hemerythrin molecules with natural cross-linker genipin, and evaluate its efficacy and safety.

Methods: Hemerythrin was isolated and purified from sipunculid worms using tangential flow ultrafiltration. Subsequently, genipin cross-linked hemerythrin nanoparticles (GHrNPs) were constructed by adding 20% w/w genipin under mildly acidic conditions, and glutaraldehyde cross-linked hemerythrin nanoparticles (GAHrNPs) were constructed by adding 10% w/w glutaraldehyde under mildly alkaline conditions. The diameter, dispersity index, zeta potential, functional group structure, P₅₀, and Hill coefficient of the two nanoparticle groups were measured. The two nanoparticle groups at different concentrations were co-cultured with vascular endothelial cells for 24 hours, then the cell viability and NO concentration in the culture medium were measured.

Results: After glutaraldehyde/genipin molecular cross-linking, infrared spectra showed the continuous presence of amide bands I and II. The hydrated particle sizes of hemerythrin, GHrNP and GAHrNP were (93.14±2.11), (109.53±3.54), and (115.65±2.65) nm, dispersity indexes were 0.30±0.06, 0.27±0.05, and 0.25±0.03, zeta potentials were (-24.00±1.54), (-19.52±1.31), and (-18.90±1.25)mV, P₅₀ values were (9.28±0.22), (8.50±0.54), and (5.75±0.90) mmHg, and Hill coefficients were 1.61±0.14, 1.58±0.17, and 1.41±0.22, respectively. The average hydrated particle size increased after cross-linking with hemerythrin, the negative value of the zeta potential decreased (both P < 0.05). The P₅₀ value of GAHrNP was significantly decreased than that of hemerythrin and GHrNP (P < 0.05). The viability of vascular endothelial cells in the GHrNP group was higher than that in the GAHrNP group at different mass concentrations (P < 0.05). The NO concentration in the culture medium of vascular endothelial cells in the GHrNP group was higher than that in the GAHrNP group only at 2.0 mg/ml (P < 0.05).

Conclusion: Hemerythrin molecules cross-linked by genipin can form stable nanoparticles with good oxygen-carrying activity and lower cytotoxicity compared to glutaraldehyde.

Objective: In order to clarify the ABO phenotype and genotype, and explore the molecular biological mechanism, serological detection, genotyping and gene sequencing were performed on an upper gastrointestinal hemorrhage patient with inconsistent forward and reverse ABO blood typing.

Methods: ABO forward and reverse blood typing, H antigen identification, capillary centrifugation test and salivary substance detection were performed by classical serological method, moreover, polymerase chain reaction-sequence specific primer (PCR-SSP) was used for ABO genotyping, ABO gene 1-7 exons were sequenced by Sanger analysis in order to identify mutation.

Results: Mixed field agglutination with anti-A, anti-AB and no agglutination with anti-A1 were appeared in the forward typing tests, agglutination with B cells but no agglutination with A1 cells and O cells were appeared in the reverse typing tests. 3+ agglutination strength was showed with anti-H. In capillary centrifugation experiment, erythrocyte after isolation in proximal part and distal end had same strength of agglutination with anti-A. Substances A and H were detected in saliva. The patient was assigned an A3 phenotype according to serological characteristics. Sequencing results of ABO gene 1-7 exons showed c.261delG, c.467C>T, c.865A>G, in which, 865A>G was the first discovered mutation, and this new mutation had been submitted to GenBank with accession number PP187306.

Conclusion: A novel site mutation c.865A>G is reported in this study, and this new mutation can result in a replacement of Met with Val at residue 289 (p.Met289Val) and lead to an A3 phenotype.

Objective: To analyze the genotypes and distribution of thalassemia in Xindu District of Chengdu, in order to provide reference for the prevention and treatment of thalassemia in this area.

Methods: A total of 3 679 samples screened for thalassemia gene in Xindu District People's Hospital of Chengdu from June 2021 to April 2024 were selected as the study objects. Blood related parameters were detected by blood analyzer, hemoglobin composition was analyzed by capillary electrophoresis, and routine thalassemia gene detection was performed by PCR + flow-through hybridization. For the samples whose hematologic characteristics did not match the conventional results of thalassemia genes, the genotypes were determined by gene sequencing technology and the results were analyzed.

Results: Among 3 679 samples, 540 carriers were detected, the total detection rate was 14.68%. Among them, 329 cases were α-thalassemia, with a total of 8 genotypes. The top 3 genotype in frequency were --^SEA/ αα (45.29%, 149/329), - α^3.7/ αα (38.91%, 128/329), and - α^4.2 / αα (6.08%, 20/329). There were 197 cases of β-thalassemia, with a total of 10 genotypes, and the top 3 genotype in frequency were β ^{CD41-42 (-TCTT)}/β ^N (29.95%, 59/197), β ^CD17(A>T)/β ^N (27.92%, 55/197), and β ^{IVSII-654(C>T)} /β ^N (24.87%, 49/197). There were 14 cases of αβ-thalassemia, with a total of 12 genotypes, and the main were - α^3.7/ αα, β ^{IVSII-654(C>T)} /β ^N and - α^3.7/ αα, β ^{CD41-42 (-TCTT)}/β ^N . There was a rare thalassemia genotype (--^SEA/ HKαα). In addition, three rare abnormal hemoglobin mutations and one unreported abnormal hemoglobin mutation (HBA1:c.300+13C>G site heterozygous mutation) were also found.

Conclusion: The detection rate of thalassemia gene in this area is high and the genotype is complex. In gene diagnosis, we should pay attention to the combination of multi-technology detection to avoid missing rare genotypes.

Objective: To investigate the bone marrow and peripheral blood cytological characteristics and prognosis in acute myeloid leukemia (AML) with FLT3-ITD mutation.

Methods: A total of 106 newly diagnosed AML patients who were hospitalized in the First Affiliated Hospital of Xi'an JiaoTong University from January 2021 to December 2023 were collected, and divided into mutation group and non-mutation group according to the results of high-throughput sequencing of bone marrow specimens. The cytological characteristics of bone marrow smears and peripheral blood smears of patients in the two groups were analyzed at the time of initial diagnosis. The differences in the degree of hyperplasia, the proportion of leukemic cells, and the erythroblasts and megakaryocytes were compared between the two groups. What's more, the relationship between FLT3-ITD mutation status and characteristics of bone marrow and peripheral blood cells was analyzed.

Results: AML patients with FLT3-ITD mutation accounted for 24.53% of the hospitalized AML patients during the same period. Patients with peripheral blood leukocyte counts >30×10⁹/L accounted for 53%, and >100×10⁹/L accounted for 15% in FLT3-ITD mutation group. Compared with non-mutation group, the peripheral blood leukocyte count was significantly higher in the mutation group ( P <0.001), and the degree of hemoglobin decline was milder (P <0.05). The level of platelet was not significantly different between the two groups (P >0.05). The highest proportion of FAB subtypes were M2a and M5a in mutation group, which accounted for 38% and 27%, respectively. The proportion of extreme hyperplasia of bone marrow in the mutation group was 38.46%, which was higher than 23.75% in the non-mutation group. The proportion of peripheral blood and bone marrow leukemic cells in patients with high-frequency mutation were significantly higher than those in patients with low-frequency mutation (both P <0.01). The complete remission (CR) rate after the first induction chemotherapy was 38.46% and 65.00% in the mutation group and non-mutation group, respectively, and the CR rate after 2 courses of induction chemotherapy was 50.00% and 73.75%, respectively.

Conclusion: The FLT3-ITD mutation results in high proliferation and rapid progression of the bone marrow feature in AML patients, with less suppression of normal erythropoiesis. Increased mutation frequency is accompanied by increased leukemic tumor burden in the bone marrow and circulation, and patients with FLT3-ITD mutation have a low response rate to early induction therapy.

Objective: To clarify the prognostic significance of 1q21 amplification in multiple myeloma (MM), and explore the efficacy and prognosis of ixazomib in the treatment of MM patients with 1q21 amplification.

Methods: A retrospective analysis of clinical data was conducted on 77 patients with newly diagnosed MM who were hospitalized in Zhongshan Hospital, Xiamen University from January 2010 to December 2022. To analyze the clinical features of MM patients with 1q21 amplification, evaluate the mitigation rate and survival treated with ixazomib-based regimens.

Results: Among the 77 newly diagnosed MM patients, 40 patients had 1q21 amplification, while 37 didn't. Multivariate Cox regression analysis revealed that 1q21 amplification was an independent risk factor affecting the prognosis of MM patients (P < 0.05). Compared to patients without 1q21 amplification, those with 1q21 amplification had poorer progression-free survival (PFS) and overall survival (OS) (both P < 0.05). When the 1q21 amplification ratio exceeded 66.7%, both PFS and OS were worse (P < 0.05). There were no statistical differences in the deep remission rate (≥VGPR), overall response rate and PFS between the 1q21 amplification positive and negative groups treated with ixazomib-based regimens (P >0.05), but OS showed a significant difference (P < 0.05). Among the patients who switched to ixazomib treatment from bortezomib, there was a statistically significant difference in the complete response rate (P < 0.05). Compared to other treatment regimens, ixazomib-based regimens resulted in a significant reduction in adverse reactions such as peripheral neuropathy (P < 0.05).

Conclusion: Ixazomib-based chemotherapy regimens can overcome the poor prognosis associated with 1q21 amplification and improve mitigation rates and PFS in patients. Ixazomib has low incidence of adverse reactions, good safety profile and prolonged duration of therapy.

Objective: To investigate the mechanism of natural antigen B (nAgB) to protect Immune thrombocytopenia (ITP) mouse model by influencing autophagy.

Methods: Twenty-eight female BALB/c mice aged 8-10 weeks were randomly divided into four groups. 7 mice of each group were immunized intraperitoneally, the control group was treated with PBS as the control group; ITP group was treated with anti-CD41 monoclonal antibody (anti-CD41Ab) only; nAgB group was treated with nAgB intraperitoneal injection for 5d; nAgB+ITP group was treated with nAgB intraperitoneal injection for 5d, then treated with anti-CD41 Ab. The peripheral blood platelet count in each group was tested; and the spleen and liver should be isolated and weighed, the organ index was calculated; qRT-PCR was used to detect spleen microtubule-associated protein 1 light chain 3 ( LC3), p62, Beclin-1 mRNA expression levels. Western blot was used to detect the protein expression level of spleen LC3Ⅱ/LC3Ⅰ, p62, Beclin-1.

Results: Compared with the control group, mice in the ITP group showed a significant decrease in blood PLT count ［(102.1±17.9)×10⁹/L vs (485.4±185.2)×10⁹/L, P <0.01］, a significant increase in spleen index (P <0.01), mice in the nAgB group showed a significant increase in blood PLT count, rising to (1051±127.6)×10⁹/L on the 3 day after modeling. Compared with the ITP group, mice in the nAgB+ITP group showed a significant increase in PLT count on the 1 day of anti-CD41 Ab administration ［(428.6±131.6)×10⁹/L vs (102.1±17.9)×10⁹/L, P <0.05］, however, the spleen index was significantly decreased (P <0.05). qRT-PCR and Western blot results showed that compared with the control group, the mRNA and protein expression levels of spleen LC3, p62 and Beclin-1 were increased in the ITP group of mice (P <0.05, P <0.01). Compared with the ITP group, the nAgB+ITP group could significantly decrease mRNA levels of spleen LC3, p62 and Beclin-1 (P <0.05, P <0.01), and also significantly decrease the protein expression levels of LC3Ⅱ/LC3Ⅰ, p62 and Beclin-1 (P <0.05, P <0.01).

Conclusion: nAgB inhibits the transcription and expression levels of autophagy-related genes and regulates immune intolerance, thereby protecting ITP mouse models.