Transcriptome-based analysis of the toxic effects of aluminum chloride exposure on spermatocytes.

Aluminum chloride (AlCl3) exposure is pervasive in our daily lives. Numerous studies have demonstrated that exposure to AlCl3 can lead to male reproductive toxicity. However, the precise mechanism of action remains unclear. The objective of this study is to investigate the mechanism of aluminum-induced toxicity by analyzing the alterations in the global transcriptome gene profile of mouse spermatocytes (GC-2spd cells) exposed to AlCl3. GC-2spd cells were exposed to concentrations of 0, 1, 2, and 4 mM AlCl3, and high-throughput mRNA-seq was performed to investigate the changes in the transcriptome after exposure to 4 mM AlCl3. Our findings indicate that exposure to AlCl3 led to an increase in oxidative stress, disrupted glutathione metabolism, reduced cell viability, and altered gene expression in mouse spermatocytes. Gene enrichment analysis revealed that the differentially expressed genes (DEGs) were associated with various biological functions such as mitochondrial inner membrane, response to oxidative stress. Furthermore, these DEGs were found to be enriched in pathways including proteasome, glutathione metabolism, oxidative phosphorylation, and Hif-1 signaling pathway. Real-time PCR and western blot were employed to validate the expression alterations of pivotal genes, and the outcomes exhibited concordance with the mRNA-seq findings. This study provides a theoretical basis for revealing the potential mechanism of male reproductive toxicity caused by aluminum exposure.

[Survival efficacy of MDS/AML patients with TP53 abnormal received allogeneic hematopoietic stem cell transplantation].

Objective: TP53-abnormal MDS/acute myeloid leukemia (AML) patients' allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment's effectiveness and influencing factors should be studied. Methods: 42 patients with TP53 gene status change MDS/AML who underwent allo-HSCT from 2014.8.1 to 2021.7.31 at the Hematology Hospital of the Chinese Academy of Medical Sciences were the subject of a retrospective analysis. The 42 patients were divided into three groups: the TP53 deletion group (group A) , TP53 mono-alle mutation group (group B) , and TP53 multi-hit group (group C) . The differences in clinical features and prognostic factors after transplantation were analyzed. Results: There were 42 MDS/AML patients, including 21 patients with MDS, and 21 patients with AML. The median follow-up period was 34.0 (7.5-75.0) months and the median patient age at the time of transplantation was 41.5 (18-63) years old. The total OS was 66.3% (95% CI 53.4%-82.4%) in 3 years after transplantation, and EFS was 61.0% (95% CI 47.7%-78.0%) in 3 years. For 3 years after receiving hematopoietic stem cell transplantation, there were no statistically significant differences in 3-year OS and EFS in groups A, B, and C (P≥0.05) . The 3 years OS was 82.5% (95% CI 63.1%-100.0%) in group A, 60.6% (95% CI 43.5%-84.4%) in group B, and 57.1% (95% CI 30.1%-100.0%) in group C. Univariate analysis revealed that the number of co-mutant genes, pre-HSCT treatment, and disease type did not affect prognosis, while age, karyotype, co-mutation, positive blast cell before transplantation, and positive blast cell after transplantation were common prognostic factors for OS and EFS (P<0.1) . MRD levels before transplantation were found to be independent risk factors for OS (P=0.037, HR=33.40, 95% CI 1.24-901.17) in a multivariate analysis. Conclusion: Patients with MDS/AML who have TP53 mutations can benefit from allo-HSCT, but patients with complex karyotypes have a worse prognosis. Meanwhile, the final flow cytometry (FCM) monitoring blast cell test before HSCT has a certain guiding significance for prognostic assessment.

New advances in targeted therapy and immunotherapy of acute myelogenous leukemia / 白血病·淋巴瘤

Acute myelogenous leukemia (AML) is a highly heterogeneous malignant hematologic disease, and it is mainly treated with traditional chemotherapy, but the efficacy is limited and the patients with worse performance status and comorbidities can not be treated with chemotherapy. Gene changes play an important role in the diagnosis and prognosis of AML, and these gene changes also provide targets for molecular targeted therapy. Meanwhlie, immunotherapy has achieved certain curative effects in AML and has a promising prospect. In this review, targeted therapy and immunotherapy of AML reported in 61st American Society of Hematology (ASH) Annual Meeting are summarized.