中国实验血液学杂志最新文献

Objective: To explore whether Ph⁺ acute lymphoblastic leukemia (ALL) cell line SUP-B15 treated with imatinib occurs a tolerant status charactered by cell proliferation suppression but apoptotic resistance, then evaluate whether IGF1-R inhibitor AEW541 can break this tolerance, and further explain its mechanisms.

Methods: SUP-B15 cells were treated with different concentrations of imatinib or AEW541. Cell proliferation was assayed by Deep Blue, and apoptotic cells were determined by Annexin V/7-AAD staining. Apoptotic rate was measured by flow cytometry after co-treatment of imatinib and AEW541. Western blot was used to evaluate ABL downstream signals, including the phosphorylation of STAT5, ERK1/2, and AKT, as well as to detect cleaved caspase-3 and PARP1, the molecular signatures of apoptosis. Furthermore, an inhibitor of STAT5 or MEK-ERK1/2 was used to confirm the key mechanism of the combination of imatinib and AEW541 induced SUP-B15 cell apoptosis.

Results: Imatinib monotherapy effectively suppressed the proliferation of SUP-B15 cells, but did not induce significant increase of apoptotic rate, leading to occurrence of tolerant status. AEW541 monotherapy did not dramatically affect the proliferation and apoptosis of SUP-B15 cells, but significantly increased apoptotic rate of SUP-B15 cells and cleavage of caspase-3 and PARP1 when combined with imatinib simultaneously. A combination of imatinib and AEW541 reduced STAT5 and ERK1/2 phosphorylation as compared with imatinib monotherapy in SUP-B15 cells, but had no impact on AKT phosphorylation.Apoptosis could be induced by STAT5 inhibitor AC-4-130, but not by MEK-ERK1/2 inhibitor trametinib in SUP-B15 cells.

Conclusion: SUP-B15 cells treated with imatinib can establish drug tolerance. IGF1-R inhibitor AEW541 can further reduce STAT5 activation, thereby boosting the effect of apoptotic induction of imatinib on SUP-B15 cells. This research may provide a new idear to overcome imatinib tolerance.

Acute myeloid leukemia (AML) is the most common and highly heterogeneous acute leukemia in adults. Despite the continuous optimization of prognostic risk stratification and treatment regimens, the overall long-term survival rate of AML patients remains low. The emergence of single cell sequencing (SCS) technology has overcome the defects of traditional sequencing to a certain extent, and realized the transformation of the research of malignant tumors from cell population level to single cell level. Consequently, it has been widely applied in many biological fields. This review mainly focuses on the application of SCS technology in the analysis of tumor heterogeneity, disease evolution, changes in tumor microenvironment, elucidation of drug resistance mechanisms and search for potential therapeutic targets in AML.

Objective: To investigate the effects of Curcumol on the malignant biological characteristics of acute myeloid leukemia (AML) cells and its molecular mechanism, and to provide theoretical and experimental evidence for the anti-leukemia treatment of traditional Chinese medicine.

Methods: After the AML cell lines HL-60 and KG-1 cells were treated different concentrations of with Curcumol. The proliferation activity of cells was detected by CCK-8 method, and the expression changes of apoptotic proteins and PI3K/AKT signaling pathway proteins were detected by Western blot. Real-time quantitative fluorescence polymerase chain reaction (RT-qPCR) was used to detect the expression of Caspase family mRNA.

Results: Curcumol could inhibit the proliferation and induce apoptosis of HL-60 and KG-1 cells, promote apoptosis by up-regulating the expression of Bax and down-regulating the expression of Bcl-2 protein (P <0.05). When Curcumol interferes with HL-60 and KG-1 cells, it can also induce programmed cell death of AML by inhibiting PI3K/AKT signaling pathway. In addition, after the intervention of Curcumol, the expression of Caspase 3, Caspase 6, Caspase 8 and Caspase 9 were up-regulated in HL-60 cells (P <0.05), the expression of Caspase 3, Caspase 8 and Caspase 9 were significantly up-regulated in KG- cells (P <0.01), while the expression of Caspase 6 was weakly affected (P <0.05), but low concentration of Curcumol (< 60 μg/ml) had no effect on the expression of Caspase 6 in KG-1 cells (P >0.05).

Conclusion: Curcumol may mediate the programmed death of AML cells by inhibiting the PI3K/AKT signaling pathway, affecting the expression of Bcl-2 family proteins, and promoting the activation of core members of Caspase family, so as to play an anti-leukemia role.

Objective: To analyze the risk factors of primary poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid malignancies and the impact of primary PGF on survival.

Methods: The clinical data of 146 patients with myeloid malignancies who underwent allo-HSCT in our hospital from January 2015 to December 2021 were retrospectively studied. Some relevant clinical parameters which may affect the development of primary PGF after allo-HSCT were selected for univariate and multivariate analysis, as well as performed survival analysis.

Results: A total of 9 patients (6.16%) were diagnosed with primary PGF, and their medium age was 37(28-53) years old. Among them, 1 case underwent matched sibling donor HSCT, 1 case underwent matched unrelated donor HSCT, and 7 cases underwent HLA-haploidentical related donor HSCT. Moreover, 5 cases were diagnosed as cytomegalovirus (CMV) infection, and 3 cases as Epstein-Barr virus (EBV) infection. Univariate and multivariate analysis showed that CD34⁺ cell dose <5×10⁶/kg and pre-transplant C-reactive protein (CRP) >10 mg/L were independent risk factors for occurrence of the primary PGF after allo-HSCT in patients with myeloid malignancies. The 3-year overall survival (OS) rate of primary PGF group was 52.5%, which was significantly lower than 82.8% of good graft function group (P < 0.05).

Conclusion: Making sure pre-transplant CRP≤10 mg/L and CD34⁺ cell dose ≥5×10⁶/kg in the graft may have an effect on preventing the occurrence of primary PGF after allo-HSCT. The occurrence of primary PGF may affect the OS rate of transplant patients, and early prevention and treatment are required.

Objective: To investigate the safety, efficacy, and prognosis of high-dose melphalan in combination with autologous hematopoietic stem cell transplantation (ASCT) for the treatment of multiple myeloma (MM).

Methods: The clinical data of 17 patients with newly diagnosed MM who underwent ASCT as first-line consolidation therapy at the Yijishan Hospital of Wannan Medical College from March 2020 to October 2022 were retrospectively analyzed. The safety, efficacy, and prognosis of this treatment approach were evaluated.

Results: Of the 17 patients, 10 were male and 7 were female, with a median age of 56 (45-64) years. The stem cell engraftment rate was 100%, with a median neutrophil engraftment time of +10 (9-12) days and a median platelet engraftment time of +12 (10-21) days. The incidence of oral mucositis and intestinal infection after transplantation was 100%, with 2 cases of pulmonary infection, 1 case of urinary tract infection, 1 case of skin infection, and 11 cases of transient elevation of serum amylase. After transplantation, 13 patients achieved a complete response (CR) or better, and the CR rate showed an increasing trend compared to before transplantation (13/17 vs 8/17; P =0.078). The median follow-up time was 18 (6-36) months, and 15 patients survived without progression, 1 patient experienced disease progression, and 1 patient died due to clinical relapse and abandonment of treatment. The 2-year overall survival (OS) rate and progression-free survival (PFS) rate were approximately 90.0% and 83.9%, respectively.

Conclusion: High-dose melphalan in combination with ASCT as first-line consolidation therapy for MM can enhance the depth of patient response, further improve therapeutic efficacy, and the transplant-related complications are controllable, making it a viable option worth promoting in clinical practice.

Objective: To analyze the dynamic changes of neutrophil percentage-to-albumin ratio (NPAR) during treatment with bortezomib-lenalidomide-dexamethasone (VRD) in patients with multiple myeloma (MM), and explore the relationship between NPAR value and short-term prognosis of MM patients.

Method: The data of 80 MM patients who underwent VRD chemotherapy at Tangshan Workers Hospital from January 2019 to April 2021 were retrospectively analyzed. NPAR levels were measured before VRD chemotherapy (T0), and on the first day of the third (T1), sixth (T2), and eighth (T3) chemotherapy cycles. All patients were followed up for 1 year, with the recurrence, progression, or death occurring within 1 year after the completion of VRD treatment as the endpoint event. The patients were divided into a good prognosis group and a poor prognosis group based on the follow-up results. The changes in NPAR at T0, T1, T2, and T3 in the two groups were statistically analyzed. The restricted cubic spline method was used to analyzed the relationship between NPAR and adverse short-term prognosis in MM patients undergoing VRD chemotherapy.

Results: Among the 80 MM patients, 25 cases (31.25%) had poor short-term prognosis, including 19 cases (23.75%) of progression or recurrence, and 6 cases (7.50%) of all-cause mortality. The levels of neutrophils and NPAR in the poor prognosis group at T0, T1, T2 and T3 were higher than those in the good prognosis group at the same period, while the albumin levels in the poor prognosis group at T0, T1, and T2 were lower than those in the good prognosis group at the same period (P < 0.05); There was no significant difference in albumin levels between the poor prognosis group and the good prognosis group at T3 (P >0.05). Within the poor prognosis group and the good prognosis group, the levels of neutrophils and NPAR decreased sequentially at T0, T1, T2, and T3, while the levels of albumin increased sequentially, and the differences between each stage were statistically significant (P < 0.05). The restricted cubic spline model showed an approximate J-shaped curve between the risk of poor short-term prognosis and the pre-treatment NPAR level in MM patients (P < 0.05). If the pre-treatment NPAR>0.52, the risk of poor short-term prognosis in MM patients increased with the increase of NPAR value.

Conclusion: After VRD treatment, the NPAR value of MM patients gradually decreases, and there is a correlation between the NPAR value before VRD treatment and the risk of poor prognosis after treatment. If NPAR>0.52 before treatment, the higher the NPAR value, the higher the risk of poor short-term prognosis in MM patients.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome (VEXAS) is a recently discovered adult-onset autoinflammatory syndrome characterized by methionine somatic mutations affecting the activation of ubiquitin system in the X-linked gene UBA1 . Patients present with a wide range of inflammatory manifestations (fever, neutrophil dermatosis, chondritis, pulmonary infiltrates, ocular inflammation, venous thrombosis) and hematological impairment (giant cell anemia, thrombocytopenia, bone marrow and pre-erythrocyte vacuoles, bone marrow dysplasia), consequently contributing to significant morbidity and mortality. Current treatment management method is not well developed, and the main existing therapies are aimed at controlling inflammatory symptoms or targeting UBA1 mutations. Symptomatic supportive care includes control risk factors (such as infection and thrombosis), component transfusion, and use of hematopoietic drugs. This review aims to summarize new advances of the pathogenesis, clinical manifestations and treatment of this disease in the past two years.

Objective: To summarize the clinical characteristics of patients with combined pneumocystis jiroveci pneumonia (PJP) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods: The clinical manifestations, laboratory tests, imaging findings, and treatment outcomes of 21 allo-HSCT patients with PJP diagnosed at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematology Hospital from July 2018 to July 2023 were retrospective analyzed.

Results: Among the 21 patients, the male -to-female ratio was 2.5∶1, and the median age was 36 years old with a range of 15-62 years. The median time to diagnosis of PJP after transplantation was 225 days. The clinical manifestations lack specificity, and the main clinical symptoms include respiratory symptoms (dyspnea, cough, sputum, etc.) and fever. Laboratory examination revealed peripheral blood lymphocyte counts decreased in 15 cases, CD4⁺ T lymphocyte absolute values less than 200 cells/μl in 19 patients, C-reactive protein levels significantly increased in 20 patients, lactate dehydrogenase levels increased in 14 patients, and 1,3-β-D-glucan detection levels increased in 14 patients. Chest CT manifestations can be divided into three types: ground glass type, nodular type, and mixed type. Among them, the incidence of ground glass type was the highest (18/21), with 2 cases of nodular type and 1 case of mixed type. The sequence number of Pneumocystis jiroveci was detected through mNGS (15-57 570), and 11 patients had mixed infections. In terms of treatment, TMP-SMX, Caspofungin, and methylprednisolone were administered, and 17 patients achieved improvement in their condition. Four patients died, all of whom died from respiratory failure.

Conclusion: PJP is a critically ill condition after hematopoietic stem cell transplantation, and diagnosis is difficult. Early diagnosis can achieve better prognosis. The sensitivity of mNGS in diagnosing PJP is high, providing the possibility of early and accurate diagnosis for clinical practice, which is worthy of application and promotion.

Objective: To investigate and assess hemolytic transfusion reaction in patient with complex and combined anti-Fy^a and anti-Jk^b which so as to provide a safety blood transfusion strategy.

Methods: ABO/Rh blood grouping, antibody screening and identification, and Coombs' tests were performed by the routine serological methods include manual tube and automatic blood group analyzer with matching micro-column gel cards from Diagnostic Grifols and Jiangsu LIBO. The hospital information system and laboratory information system were used to collect dada on patients' blood routine tests, liver and kidney function, coagulation, cardiac function, and other clinical indicators before and after blood transfusion were analyzed and compared in conjunction with the patients' clinical manifestations.

Results: The patient's blood group was A/CcDEe. Before two transfusion, the anti-body screening were positive which identification were anti-Fy^a and anti-Fy^a combined with anti-Jk^b respectively, while the Coomb's test were positive with anti-C₃ and anti-IgG combined with anti-C₃ respectively. No agglutination and hemolysis was observed in saline medium cross-matching test before two transfusion of Fy^a- red blood cell. But before re-transfusion agglutinated reaction was observed in cross-matching test by DG Gel ^®Coombs, which strength was 2+ on whether major or minor side. The patient developed soy sauce urine/hemoglobinuria and fever after transfused Fy^a- red blood cell again. Primary laboratory indicators were observed to be elevated, include C-reactive protein from 3.06 mg/L to 29.97 mg/L, total bilirubin from 21.4 μmol/L to 276.3 μmol/L, direct bilirubin from 8.4 μmol/L to 135.6 μmol/L, lactate dehydrogenase from 166 U/L to 1453 U/L. Urinary free hemoglobin test was 4+. The main laboratory indicators reflecting the heart, liver, kidney and circulatory coagulation function also have vary increased and gradually returned to normal after a week.

Conclusion: Jk^b-incompatible transfusion of the Kidd blood group system can lead to acute hemolytic transfusion reaction, but in emergency implementing incompatible transfusion due to IgG antibodies outside of the primary blood group (such as ABO/RhD) can ensure the implementation of emergency operation.