Objective: To investigate the expression of serum histone deacetylase 2 (HDAC2) in patients with acute myeloid leukemia (AML) and its clinical significance.
Methods: The 150 AML patients who received treatment in our hospital from April 2017 to April 2019 were included as AML group, and further divided into survival group (108 cases) and death group (42 cases) according to their survival status. In addition, 100 health individuals undergoing health examination in the same period were included as control group. The expression of HDAC2 in serum was detected by real-time quantitative PCR. Cox regression was used to analyze the influencing factors of adverse prognosis. The predictive effect of serum HDAC2 for the adverse prognosis of AML patients was evaluated by the receiver operating characteristic (ROC) curve.
Results: Compared with the control group, the expression of serum HDAC2, interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β and C-reactive protein (CRP) in AML group was obviously increased (all P <0.05). Compared with the survival group, the expression of serum HDAC2 in the death group was also increased (P <0.05). Serum HDAC2 was positively correlated with IL-6, TNF-α, IL-1β and CRP in AML patients (r =0.567, 0.559, 0.623, 0.537). According to Cox regression analysis, the IL-6, TNF-α, IL-1β and HDAC2 were independent risk factors affecting the prognosis of AML patients (all P <0.05). ROC analysis showed that the AUC of serum HDAC2 level in predicting the adverse prognosis of AML was 0.862.
Conclusion: The expression level of serum HDAC2 in AML patients is increased, which has positive correlations with IL-6, TNF-α, IL-1β and CRP. HDAC2 is an independent risk factor for the poor prognosis of AML patients, and has a high predictive value.
Objective: To analyze the clinical characteristics and prognosis of children with hypodiploid B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Methods: The clinical data of 1 287 children with BCP-ALL admitted to five hospital in Fujian province from April 2011 to December 2020 were retrospectively analyzed. According to the results of chromosome karyotype, all the patients were grouped into hypodiploid subgroup and non-hypodiploid subgroup. The clinical characteristics, early treatment response ［minimal residual disease (MRD) on middle stage of induction chemotherapy and end of induction chemotherapy］ and long-term efficacy ［overall survival (OS) and event-free survival (EFS)］ were compared. The prognostic factors of hypodiploid BCP-ALL were further explored.
Results: Among 1 287 BCP-ALL patients， 28 patients (2.2%) were hypodiploid BCP-ALL. The proportion of patients with white blood cell count （WBC）≥50×109/L in the hypodiploid subgroup was significantly higher than that in the non-hypodiploid subgroup (P =0.004), while there was no statistically significant difference in gender ratio, age group at initial diagnosis, and early treatment response between the two groups (all P >0.05). The 5-year EFS and OS rate of the hypodiploid subgroup were 75.0%(95%CI ：66.8%-83.2%) and 77.8%(95%CI ：69.8%-85.8%), respectively, which were lower than those of non-hypodiploid subgroup ［EFS: 79.6%(95%CI ：78.4%-80.8%); OS: 86.4%(95%CI ：85.4%-87.5%)］, but the difference was not statistically significant (all P >0.05). Further subgroup analysis by risk stratification showed that the 5-year EFS and OS rates of the hypodiploid subgroup were significantly lower than those in the low-risk (LR) group ［LR group EFS: 91.4% (95%CI ：88.4%-93.6% ), P < 0.001; OS: 94.7% (95%CI ：92.1%-96.4%), P < 0.001］ ; it was similar to that of BCP-ALL children stratified into intermediate-risk (IR) excluding hypodiploid ［IR group EFS: 79.4%(95%CI ：74.9%-83.2%), P =0.343; OS: 87.3%(95%CI ：83.6%-90.2%), P =0.111］; while was higher than that of EFS in HR group, but the difference was not statistically significant ［HR group EFS: 58.7%(95%CI ：52.6%-64.8%), P =0.178. OS: 69.9%(95%CI ：63.5%-75.4%), P =0.417］. Univariate analysis showed that gender, age, white blood cell count, and MRD on middle stage of induction chemotherapy had no significant impact on OS and EFS; chromosome count< 40 was a risk factor for lower OS (P =0.026), but has no significant effect on EFS; MRD≥0.01% after induction therapy was a risk factor for lower OS and EFS (P =0.002, and 0.001, respectively).
Conclusion: Children with hypodiploid BCP-ALL have an intermediate prognosis, and MRD ≥0.01% after induction chemotherapy may be a risk factors for poor prognosis.
Objective: To investigate the effect of endothelial activation and stress index (EASIX) on the prognosis of patients with angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), and to compare the clinical characteristics of patients in the low EASIX and high EASIX groups.
Methods: The clinical data of 59 newly diagnosed AITL and PTCL-NOS patients admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to September 2021 were retrospectively analyzed. The optimal cut-off value of EASIX was determined by receiver operating characteristic (ROC) curve; The chi-square test was used to analyze the correlation between EASIX and clinical features of patients with AITL and PTCL-NOS; The Kaplan-Meier survival curve was used to analyze the overall survival (OS) and progression-free survival (PFS) of the patients; Univariate and multivariate analyses were performed by using Cox proportional hazards model.
Results: The optimal cut-off value of EASIX was 0.95, based on which the patients were divided into a low EASIX (<0.95) group and a high EASIX (≥0.95) group. Compared with the low EASIX group, the high EASIX group had a higher proportion of patients with advanced Ann Arbor stage, higher risk according to IPI, elevated LDH, hypoproteinemia, anemia, B symptoms,extranodal involvement, and bone marrow involvement. Survival analysis showed that the OS and PFS of patients in the high EASIX group were significantly shorter than those in the lower EASIX group(P <0.001). The multivariate analysis showed that EASIX was an independent risk factor for OS ［HR=7.217 (95%CI : 1.959-26.587), P =0.003］ and PFS ［HR=2.718(95%CI : 1.032-7.161), P =0.043］ of PTCL patients.
Conclusion: High EASIX in newly diagnosed patients with AITL and PTCL-NOS suggests a poor prognosis, and high EASIX is a risk factor affecting prognosis of the patients.
Objective: To analyze the effect of peripheral blood hematopoietic stem cells (PBSC) collection from unrelated donors and its influencing factors.
Methods: A retrospective analysis was conducted on the mobilization and collection of PBSC from 113 unrelated donors at Yueyang Central Hospital from January 2021 to December 2023.
Results: 113 donors were successfully mobilized. The average count of PBSC mononuclear cells (MNC) and CD34+ cells were (12.40±7.41)×108/kg and (10.64±8.07)×106/kg, respectively. Univariate analysis showed that the PBSC CD34+ cells ratio of male donors was significantly higher than that in female donors (P =0.015). The peripheral blood (PB) white blood cell (WBC) count before collection was positively correlated with the PBSC nucleated cells count (r =0.388), and the donor's body weight, the PB CD34+ cell ratio before collection were positively correlated with the PBSC CD34+ cell ratio (r =0.259, r =0.780). The daily dose of rhG-CSF was negatively correlated with the PBSC CD34+ cell ratio (r =-0.285). Both rhG-CSF agents achieved successful mobilization. Multivariate analysis showed that PB WBC count before collection was a factor affecting the count of PBSC nucleated cells (P <0.001), while the PB CD34+cell ratio before collection was a factor affecting the PBSC CD34+ cell ratio (P <0.001).
Conclusion: The mobilization and collection of PBSC from unrelated donors are good, and the PB WBC count and CD34+ cell ratio before collection are reliable indicators for predicting the collection effect.
Objective: To analyze the effects of highdose methotrexate (HD-MTX) and lenalidomide as central nervous system (CNS) prophylaxis strategies in patients with diffuse large B-cell lymphoma (DLBCL).
Methods: The data of DLBCL patients with high risk of CNS recurrence who were initially treated in Fujian Provincial Hospital and Fujian Cancer Hospital from January 2012 to June 2022 were analyzed retrospectively. The patients were divided into HD-MTX group and lenalidomide group according to different prophylaxis strategies. Each group was further divided into high-risk group and medium-risk group based on CNS-IPI score and/or testicular involvement. The CNS relapse-free survival (CRFS) rate, adverse effects, and the effects of different prophylaxis strategies on overall survival (OS) rate and progression-free survival (PFS) rate were evaluated in different groups and subgroups.
Results: There were 200 patients enrolled in this study, 80 cases in lenalidomide group and 120 cases in HD-MTX group. According to the delivery timing of prophylactic HD-MTX, the patients in HD-MTX group were further divided into two groups: 80 cases at the end of induction chemotherapy and 40 cases during chemotherapy interval. At a median follow-up of 48(14-133) months, the 4-year CRFS rate, 4-year PFS rate, and 4-year OS rate of the HD-MTX group was 93.6%, 57.2%, and 68.8%, respectively, while that of the lenalidomide group was 90.4%, 69.4% and 75.6%. There were no significant differences in 4-year CRFS rate, 4-year PFS rate, and 4-year OS rate between HD-MTX group and lenalidomide group (all P >0.05), but lenalidomide group showed a trend of improvement in PFS. Further subgroup analysis showed that there was no significant difference in 4-year CRFS rate between high-risk patients of the two groups (91.7% vs 83.4%, P >0.05), while 4-year PFS rate showed difference (49.5% vs 64.2%, P <0.05). A total of 248 cycles were collected for adverse reaction analysis in the HD-MTX group, and 25 cycles occurred neutropenia accompanied with infection (10.1%), while in lenalidomide group 240 cycles were collected in which 20 cycles occurred neutropenia accompanied with infection (8.3%). Both the two groups had no treatment-related deaths.
Conclusion: Compared with HD-MTX, lenalidomide combined with immunochemotherapy can prevent CNS relapse, at the same time, improve prognosis, which is a safe and well tolerated central prophylaxis strategy.
Primary immune thrombocytopenia (ITP) is an autoimmune disease characterized by thrombocytopenia, and T cell immune dysfunction plays an important role in the formation of ITP. As a thrombopoietin receptor agonist (TPO- RA), eltrombopag can not only directly stimulate megakaryocytes to produce platelets, but also play an immunomodulatory role by inducing regulatory T cell generation and reducing proinflammatory factors. As a second-line treatment drug for adult ITP, eltrombopag is increasingly widely used in clinical practice. This review summarized the latest research progress on the mechanism of action, efficacy, safety, and how to reduce the dosage of eltrombopag in ITP.
Objective: To investigate the effects of down-regulation of p21 activated kinase 1 (PAK1) on the proliferation, differentiation, and apoptosis of myeloproliferative neoplasm (MPN) cells (6133/MPL) with thrombopoietin receptor MPL mutation at codon 515 (MPLW515L) and survival of 6133/MPL mice.
Methods: Interference with the protein level of PAK1 in 6133/MPL cells was assessed using lentivirus-mediated shRNA transfection technology. CCK-8 assay was used to detect the effect of down-regulation of PAK1 on the proliferation viability of 6133/MPL cells, and colony-forming ability was measured by cell counting. Flow cytometry was used to detect the PAK1 kinase activity on the ability of polyploid DNA formation and cell apoptosis in 6133/MPL cells. The expression of cyclin D1, cyclin D3 and apoptosis-related protein Bax was detected by Western blot. The infiltration of tumor cells in spleen and bone marrow of 6133/MPL mice were detected by HE staining.
Results: Down-regulation of PAK1 inhibited the proliferation and reduced the ability of cell colony formation of 6133/MPL cells. After knocking down PAK1, the content of polyploid DNA in 6133/MPL cells increased from 31.8 to 57.5% and 48.0%, and the proportion of apoptosis increased approximately to 10.8%. Down-regulation of PAK1 led to a reduction of infiltration of tumor cells in liver and bone marrow of 6133/MPL mice, thereby prolonging survival time.
Conclusion: Down-regulation of PAK1 can significantly inhibit the growth of 6133/MPL cells, promote the formation of polyploid DNA, induce 6133/MPL cell apoptosis, and prolong the survival time of 6133/MPL mice.
Objective: RS4;11 cell line was used to establish BCL-2 inhibitor-resistant cell lines of B-cell acute lymphoblastic leukemia (B-ALL) and explore the possible mechanisms of drug resistance.
Methods: RS4;11 cell line was continuously induced and cultured by low and ascending concentrations of BCL-2 inhibitors navitoclax and venetoclax to construct navitoclax-resistant cell line RS4;11/Nav and venetoclax-resistant cell line RS4;11/Ven. The cell viability was detected by MTT assay, and the cell apoptosis was detected by flow cytometry. Differentially expressed genes (DEGs) between RS4;11 drug-resistant cell lines and parental cell line were detected by transcriptome sequencing technology (RNA-seq), and mRNA expression levels of DEGs between drug-resistant cell lines and parental cell line were detected by real-time PCR (RT-PCR). Western blot was used to detect the expression levels of BCL-2 family anti-apoptotic proteins in drug-resistant cell lines and parental cell line.
Results: The drug-resistant cell lines RS4;11/Nav and RS4;11/Ven were successfully established. The resistance index (RI) of RS4;11/Nav to navitoclax and RS4;11/Ven to venetoclax was 328.655±47.377 and 2 894.027±300.311, respectively. The results of cell apoptosis detection showed that compared with the drug-resistant cell lines, RS4;11 parental cell line were significantly inhibited by BCL-2 inhibitors, while the apoptosis rate of drug-resistant cell lines was not affected by the drugs. Western blot assay showed that the expression of anti-apoptotic proteins of BCL-2 family did not increase significantly in drug-resistant cell lines. RNA-seq, RT-PCR and Western blot assays showed that the expression of EP300 in drug-resistant cell lines was significantly higher than that in parental cell line (P <0.05).
Conclusion: Drug-resistant B-ALL cell lines could be successfully established by exposing RS4;11 cell line to the ascending concentration of BCL-2 inhibitors, and the drug resistance mechanism may be related to the overexpression of EP300.
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