中国实验血液学杂志最新文献

Objective: To investigate the early predictive value of halving time (HT) of BCR-ABL^IS for deep molecular response (DMR) in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitor (TKI).

Methods: The continuous data of newly diagnosed CML patients with complete case data and first-line imatinib treatment admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2014 to June 2022 were retrospectively analyzed. Combined with the clinical characteristics of the patients and the efficacy analysis at each time point, a logistic regression model was used to explore the independent influencing factors of DMR, and combined HT of BCR-ABL^IS with BCR-ABL^IS level at 3 months to predict DMR of the patients.

Results: Univariate and multivariate analyses showed that HT and 3-month BCR-ABL^IS levels were independent influencing factors for MR4, MR4.5, and stable MR4.5 ( P < 0.05). ROC curve analysis determined that the best cut-off value of HT was 28 days. Compared with patients with HT>28 d, patients with HT≤28 d were more likely to obtain DMR at 2, 3, and 5 years, respectively (74.2% vs 27.3%, 71.2% vs 22.7%, and 63.6% vs 25.0%, all P < 0.001). The patients were divided into 4 groups according to BCR-ABL^IS levels at 3 months and HT. Kaplan-Meier analysis showed that the patients in the BCR-ABL^IS≤10% and HT≤28 d group had a higher probability of obtaining cumulative MR4 and MR4.5 than those in the BCR-ABL^IS≤10% and HT>28 d group (P < ＜0.05); Patients in the BCR-ABL^IS>10% and HT≤28 d group had a higher probability of obtaining cumulative MR4 and MR4.5 than those in the BCR-ABL^IS＞10% and HT>28 d group ( P < 0.05).

Conclusion: In addition to BCR-ABL^IS level, HT of BCR-ABL^IS can be used as another important predictor of treatment efficacy in CML patients. The combination of BCR-ABL^IS level and HT has a more accurate predictive value for long-term molecular response of CML patients after TKI treatment.

Objective: To investigate the molecular mechanism and distribution characteristics of RhD negative phenotypes in Han population of blood donors in Wuhu city.

Methods: A total of 210 RhD^- samples from August 2021 to August 2022 were screened by serological test and collected from Wuhu Central Blood Station for the voluntary blood donor population. Exons 1 and 10 of the RHD gene were amplificated by PCR to determine whether the samples had the RHD gene. Exons 1-10 of the RHD gene were amplificated by PCR and zygosity analysis were performed in 82 samples containing D gene, and Sanger sequencing was performed on 55 samples containing all RHD exons to determine the genotype.

Results: Among 210 RhD^- specimens, 128 cases (60.38%) had RHD gene deletion. 27 cases had partial exons of RHD, including 2 cases with RHD*DVI.3/RHD*01N.01, 24 cases with RHD*01N.04/RHD*01N.01, and 1 case with RHD-CE(2-10)/RHD*01N.01. 55 cases had retained all of 10 exons, including 4 cases with RHD*01/RHD*01N.01, 6 cases with RHD*15/RHD*01N.01, 1 case with RHD*01W.72/RHD*01N.01, 1 case with RHD*15/RHD*01EL.01, 39 cases with RHD*01EL.01/RHD*01N.01, and the remaining 4 cases were determined to have no RHD gene deletion by zygosity analysis and sequencing showed the presence of 1227G>A mutation loci.

Conclusion: There is polymorphism in the molecular mechanism of RhD^- D gene in Wuhu blood donor population, among which RHD*01EL.01 and RHD*15 are the main variants in this region. The results of this study provide a theoretical basis for RhD blood group identification and clinical blood transfusion in this region.

Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal disorders originating from hematopoietic stem cells, characterized by hemocytopenia and a high risk of transformation to acute myeloid leukemia (AML). The expected survival time of MDS patients varies widely, and accurate prognostic assessment is particularly important. Currently, patients with MDS are usually classified into a higher-risk group (HR-MDS) and a lower-risk group (LR-MDS) based on clinical prognostic scoring systems, but these scoring systems have certain limitations. Patients with LR-MDS account for 2/3 of MDS patients, with a lower risk of disease progression and a better prognosis, and their treatment mainly relies on erythropoiesis-stimulating agents, immunosuppressants and component transfusion. However, some LR-MDS patients still have poor prognosis, and the existing prognostic scoring systems cannot accurately evaluate their prognosis. In this review, the potential factors that may influence the prognosis of MDS patients beyond the existing assessment criteria were briefly summarized, with the aim of providing reference for the prognosis evaluation and treatment of LR-MDS patients.

Objective: To establish a morphologic classification system for characterizing blast cells in patients with acute promyelocytic leukemia (APL) and analyze the correlation of different APL morphologic characteristics with conventional tests and genetic variants.

Methods: Based on the morphological characteristics of APL blast cells, a classification system of 14 categories was established to characterize the inter- and intra-individual cellular morphological heterogeneity of patients. The classification system was used for the morphological analysis of 40 APL patients, and the classification results were statistically analyzed with the patients' conventional test indexes and gene variant characteristics to analyze the correlation of different APL blast cell morphological features with conventional test indexes and gene variants.

Results: In the FLT3-ITD mutation-positive group, there were significantly fewer cells with regular nuclear shape, hyper granularity, and missing Auer rods (category 1) than in the FLT3 mutation-negative group (P < 0.05). The activated partial thromboplastin (APTT) was significantly longer in the group with regular nucleus compared to the group with irregular nucleus (P < 0.05). In the hypo-granular group, the APTT was also significantly longer compared to the hyper-granular group (P < 0.01), and the proportion of myeloid blast cells was relatively lower (P < 0.05). The peripheral blood white blood cell counts, D-dimer, lactate dehydrogenase and proportion of bone marrow blast cells were significantly higher in the Auer rods (-) group than Auer rods increasing group (all P < 0.05).

Conclusion: The newly established morphologic classification system in this study can objectively characterize different types of APL blast cells, which helps to better assess the intra- and inter-individual heterogeneity of APL blast cells, and further use in accurately analyzing the correlation of morphological phenotypes with biological properties of APL.

Objective: To explore the value of REG3α, sST2 and TNFR1 in peripheral blood for risk stratification and prognostic evaluation of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children.

Methods: From January 2020 to March 2022, 70 children with aGVHD after allo-HSCT in the First Affiliated Hospital of Zhengzhou University were selected as the research objects, of which 50 cases were mild aGVHD (grade I-II) and 20 cases were severe aGVHD (grade III-IV). 30 healthy children who underwent physical examinations in our hospital during the same period were selected as the control group. Luminex platform was used to detect the protein expression levels of REG3α, sST2 and TNFR1 during aGVHD occurrence, and the differences between the three groups were analyzed by one-way ANOVA. According to the outcome of aGVHD treatment within 28 days, the patients were divided into a good prognosis group of 58 cases and a poor prognosis group of 12 cases. The ROC curve was used to analyze the value of REG3α, sST2 and TNFR1 in predicting the prognosis of children with aGVHD.

Results: The peripheral blood levels of REG3α, sST2 and TNFR1 in the mild aGVHD and severe aGVHD groups were significantly higher than those in the control group (P <0.05), and those in the severe aGVHD group were significantly higher than those in the mild aGVHD group (P <0.05). Compared with the good prognosis group, the peripheral blood levels of REG3α, sST2 and TNFR1 in the poor prognosis group were significantly higher ( t =9.27,3.33,2.97; P <0.01). ROC curve analysis showed that the area under the curve (AUC), sensitivity and specificity of the combined detection of REG3α, sST2 and TNFR1 in predicting the prognosis of children with aGVHD were higher than those of the above indicators detected alone or in pairs.

Conclusion: The expression levels of REG3α, sST2 and TNFR1 were related to the severity of aGVHD. The combination of REG3α, sST2 and TNFR1 has a high clinical value in predicting the prognosis of children with aGVHD, which is expected to provide a reliable reference for clinical evaluation of the prognosis of children with aGVHD.

Objective: To explore the clinical characteristics and prognosis of patients with diffuse large B-cell lymphoma (DLBCL) of the breast.

Methods: The clinical data of 28 DLBCL patients admitted to Shanxi Provincial Cancer Hospital from January 2013 to January 2023 were retrospectively analysed, including 13 cases of primary breast DLBCL (PB-DLBCL) and 15 cases of secondary breast DLBCL (SB-DLBCL), and the data of their clinical manifestations, laboratory tests, pathological examinations, treatment protocols, and follow-up were statistically analyzed.

Results: There were significant differences in IPI score, LDH level and β₂- microglobulin between PB-DLBCL and SB-DLBCL patients (P < 0.05). Among the 23 patients with breast DLBCL who received regular treatment, 13 patients achieved complete remission (9 patients with PB-DLBCL and 4 patients with SB-DLBCL) after initial treatment. By the end of follow-up, 11 patients relapsed or progressed (5 patients with PB-DLBCL and 6 patients with SB-DLBCL) and 9 patients died (3 patients with PB-DLBCL and 6 patients with SB-DLBCL). The 5-year OS rate was (75.0±15.3)% in PB-DLBCL group and (32.3±17.1)% in SB-DLBCL group. The 5-year PFS rate was （59.1±19.8）% in PB-DLBCL and 0% in SB-DLBCL group. The 5-year OS rate and PFS rate of PB-DLBCL patients were higher than those of SB-DLBCL patients (P < 0.05); the 5-year OS rate of the combined central preventive treatment group was higher than that of the chemotherapy group (P < 0.05).

Conclusion: Breast DLBCL is divided into two categories: PB-DLBCL and SB-DLBCL. Compared with SB-DLBCL, PB-DLBCL has the characteristics of lower IPI score, LDH, and β₂-microglobulin levels. PB-DLBCL patients have a longer survival period. In addition, the prognosis of patients receiving central preventive treatment is more optimistic.

Objective: To investigate the protective effect of endogenous ω-3 polyunsaturated fatty acid (PUFA) against cisplatin-induced myelosuppression and the mechanism of reducing apoptosis in bone marrow nucleated cells using mfat-1 transgenic mice.

Methods: The experimental animals were divided into 4 groups: wild-type mice normal control group, mfat-1 transgenic mice normal control group, wild-type mice model group and mfat-1 transgenic mice model group. The mice in the model group were injected intraperitoneally with 7.5 mg/kg cisplatin on day 0 and day 7 to construct a myelosuppression model, while the mice in the normal control group were injected intraperitoneally with an equal amount of saline, and their status was observed and their body weight was measured daily. Peripheral blood was taken after 14 day for routine blood analysis, and the content and proportion of PUFA in peripheral blood were detected using gas chromatography. Bone marrow nucleated cells in the femur of mice were counted. The histopathological changes in bone marrow were observed by histopathological staining. The apoptosis of nucleated cells and the expression level changes of apoptosis-related genes in the bone marrow of mice were detected by flow cytometry and fluorescence quantitative PCR.

Results: Compared with wild-type mice, mfat-1 transgenic mice showed significantly increased levels of ω-3 PUFA in peripheral blood and greater tolerance to cisplatin. Peripheral blood analysis showed that endogenous ω-3 PUFA promoted the recovery of leukocytes, erythrocytes, platelets and haemoglobin in peripheral blood of myelosuppressed mice. The results of HE staining showed that endogenous ω-3 PUFA significantly improved the structural damage of bone marrow tissue induced by cisplatin. Flow cytometry and PCR showed that, compared with wild-type mice model group, the apoptosis rate of bone marrow nucleated cells in mfat-1 transgenic mice was significantly reduced ( P < 0.001), and the expression of anti-apoptotic genes Bcl-2 mRNA was significantly increased ( P < 0.01), while the expressions of pro-apoptotic genes Bax and Bak mRNA were significantly reduced ( P < 0.001, P < 0.05).

Conclusion: Endogenous ω-3 PUFA can reduce cisplatin-induced apoptosis in bone marrow nucleated cells, increase the number of peripheral blood cells and exert a protective effect against cisplatin-induced myelosuppression by regulating the expression of apoptosis-related genes.

Objective: To investigate the clinical characteristics and treatment of patients with CD4⁺CD8^- T-cell large granular lymphocytic leukemia (T-LGLL).

Methods: The clinical manifestations, diagnosis and treatment of 1 case of CD4⁺CD8^- T-LGLL patient were reported, and relevant literatures were reviewed.

Results: The patient was a 70-year-old woman with slow clinical progress, mainly manifested by thrombocytopenia and myelodysplasia. The blood smear was mainly composed of large granular lymphocytes. Immunotyping and T-cell receptor gene rearrangement analysis showed that it was in line with T-LGLL. Partial remission(PR) was achieved through the treatment of cyclophosphamide(50 mg/d) combined with prednisone(gradually reduced and stopped later).

Conclusion: CD4⁺CD8^- T-LGLL is very rare in clinical practice, and its clinical manifestations are different from those of CD4^-CD8⁺ T-LGLL.

Objective: To explore the effect of heterozygous deletion of histone methyltransferase Kmt2c gene on the hematological system of mice.

Methods: CRISPR/Cas9 technology was used to construct mice model of Kmt2c heterozygous deletion (Kmt2c^+/-) and the changes of whole blood cell count in mice were continuously monitored by blood routine test. The clonal expansion ability of bone marrow cells was explored by colony formation assay in vitro and the proportion of primitive hematopoietic cells, including long-term hematopoietic stem cell (LT-HSC), short-term hematopoietic stem cell (ST-HSC), and multipotent progenitor cell in mutant mice was analyzed by flow cytometry.

Results: Kmt2c^+/- mice model was successfully constructed, and the mRNA expression level of Kmt2c was 28% of that of C57BL/6J mice. The colony formation ability of bone marrow cells of Kmt2c^+/- mice in vitro increased with the passage times, and the colony number in the fourth generation was significantly higher than that of control group (P <0.05). The proportions of LT-HSC and ST-HSC in the primitive hematopoietic cell population of Kmt2c^+/- mice was 19.6%±3.3% and 28.9%±4.9%, respectively, which showed an increasing trend compared with 16.9%±2.6% and 18.9%±2.5% in control group, but the difference was not statistically significant (P >0.05). The white blood cell count of Kmt2c^+/- mice gradually increased after 12 weeks of monitoring and reached (9.8±1.0)×10⁹/L at the 14^th week, which was significantly higher than (7.3±1.4)×10⁹/L of control group (P < 0.05).

Conclusion: The bone marrow cells of Kmt2c^+/- mice have potential of clonal expansion.

Objective: To analyze the clinical characteristics and prognosis of patients with co-mutation of CEBPA gene and GATA2 gene, so as to facilitate clinicians to formulate more accurate individualized treatment plans for patients.

Methods: A total of 43 acute myeloid leukemia (AML) patients with CEBPA double mutations and CEBPA-bZIP domain mutation admitted to the First Affiliated Hospital of Harbin Medical University from January 2017 to April 2022 were included, and the clinical characteristics and prognosis of patients with GATA2 gene mutation among them were compared and analyzed.

Results: The median age of patients with GATA2 gene mutation was 48.0 years, which was significantly lower than 57.0 years of patients without GATA2 gene mutation (P < 0.05). However, there were no significant differences in sex, white blood cell count, hemoglobin concentration, platelet count, immunophenotype, bone marrow and peripheral blood blast cell ratio and complete remission rate between the two groups (P >0.05). The median overall survival and event-free survival time of patients with GATA2 gene mutation were not reached, while those of patients without GATA2 gene mutation were 14.8 and 8.1 months, respectively (both P < 0.05).

Conclusion: The median age of patients with GATA2 gene mutation is lower than that of patients without GATA2 gene mutation. GATA2 gene mutation further prolongs the survival time of AML patients with CEBPA double mutations and CEBPA-bZIP domain mutation.