血液科学(英文)最新文献

B-cell acute lymphoblastic leukemia (B-ALL) is a malignant tumor originating from B-lineage lymphoid precursor cells. The incidence of B-ALL is about 80% in childhood acute leukemia and 20% in adults. In recent years, with standardized treatment guided by risk stratification, the long-term disease-free survival rate of children is about 80%, while that of adults is less than 40%. However, the specific pathogenesis of the newly identified B-ALL and the targeted therapy strategies have not been vigorously investigated. In this review, we highlight the recent breakthroughs in mechanistic studies and novel therapeutic options in DUX4- and MEF2D-subtype B-ALLs.

Children with sickle cell disease (SCD) are particularly prone to pneumococcal infection and administration of Prevenar 13 pneumococcal vaccine in Nigerian children with SCD is yet to be wide spread. This call for the need to study humoral immune responses stimulated by Prevenar 13 pneumococcal vaccine in SCD children to confirm the benefit or otherwise for the use of Prevenar 13 pneumococcal vaccine.

Method: The levels of humoral (innate and adaptive) immune factors and associated nutritionally essential trace elements were determined following Prevenar 13 pneumococcal vaccination of 23 Nigerian children with SCD. Serum innate humoral immune factors [Complement factors (C1q and C4), transferrin, ferritin, and C-reactive protein (CRP)] and adaptive humoral immune factors [IgG, IgA, IgM, and IgE] were determined using ELISA. Nutritionally essential trace elements such as iron (Fe), copper (Cu), and zinc (Zn) were measured also using an atomic absorption spectrophotometer.

Results: The serum levels of certain innate humoral immune factors (ferritin, CRP, and C4), only one adaptive humoral immune factors (IgE), and essential trace elements (Fe, Zn, and Cu) were significantly elevated in children with SCD post Prevenar 13 pneumococcal vaccination when compared to prevaccination levels.

Conclusion: Vaccination of children with SCD with Prevenar 13 pneumococcal vaccine was associated with increased levels of more innate humoral immune factors than adaptive factors. This study thus supports the administration of Prevenar 13 pneumococcal vaccination to children with SCD.

Defects in centrosomes are associated with a broad spectrum of hematological malignancies, such as leukemia and lymphoma. Centrosomes in these malignancies display both numerical and structural aberrations, including alterations in the number and size of centrioles, inappropriate post-translational modification of centrosomal proteins, and extra centrosome clustering. There is accumulating evidence that centrosome defects observed in hematological malignancies result from multiple factors, including dysregulation of the centrosome cycle and impairment of centriole biogenesis. In this review, we discuss the plausible mechanisms of centrosome defects and highlight their consequences in hematological malignancies. We also illustrate the latest therapeutic strategies against hematological malignancies by targeting centrosome anomalies.

To investigate the risk factors for cytomegalovirus (CMV) infection within 100 days and the relationship between early CMV infection and 1-year relapse for patients with acute leukemia following allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods: Three hundred fifty-nine patients with acute leukemia who received allo-HSCT at our center between January 2015 and January 2020 were retrospectively reviewed.

Results: Of 359 patients, 48.19% (173) patients experienced CMV infection within 100 days posttransplantation. In univariate and multivariate logistic analysis, haploidentical-related donor (HRD) (P < 0.001; odds ratio [OR], 5.542; 95% confidence interval [CI], 3.186-9.639), and ratio of CD3⁺CD8⁺ cells in lymphocytes <14.825% (P < 0.001; OR, 3.005; 95% CI, 1.712-5.275) were identified as 2 independent risk factors. One-year relapse rate (RR) between the CMV infection group and the non-CMV infection group was not statistically significant (18.5% vs 19.9%, P = 0.688). When we divided the total cohort into AML, ALL, and MAL subgroups, there were no significant differences as well (P = 0.138; P = 0.588; P = 0.117; respectively).

Conclusion: In conclusion, donor type (HRD) and the insufficient recovery of CD3⁺CD8⁺ cells were independent risk factors for CMV infection within 100 days posttransplantation in patients with acute leukemia. CMV infection within 100 days did not influence the incidence of relapse in 1 year for patients with acute leukemia.

RNA-binding proteins (RBPs) are widely involved in the transcriptional and posttranscriptional regulation of multiple biological processes. The transcriptional regulatory ability of RBPs was indicated by the identification of chromatin-enriched RBPs (Che-RBPs). One of these proteins, KH-type splicing regulatory protein (KHSRP), is a multifunctional RBP that has been implicated in mRNA decay, alternative splicing, and miRNA biogenesis and plays an essential role in myeloid differentiation by facilitating the maturation of miR-129. In this study, we revealed that KHSRP regulates monocytic differentiation by regulating gene transcription and RNA splicing. KHSRP-occupied specific genomic sites in promoter and enhancer regions to regulate the expression of several hematopoietic genes through transcriptional activation and bound to pre-mRNA intronic regions to modulate alternative splicing during monocytic differentiation. Of note, KHSRP had co-regulatory effects at both the transcriptional and posttranscriptional levels on MOGOH and ADARB1. Taken together, our analyses revealed the dual DNA- and RNA-binding activities of KHSRP and have provided a paradigm to guide the analysis of other functional Che-RBPs in different biological systems.

N⁶-Methyladenosine (m⁶A) is the most abundant modification in eukaryotic mRNA, and plays important biological functions via regulating RNA fate determination. Recent studies have shown that m⁶A modification plays a key role in hematologic malignancies, including acute myeloid leukemia. The current growth of epitranscriptomic research mainly benefits from technological progress in detecting RNA m⁶A modification in a transcriptome-wide manner. In this review, we first briefly summarize the latest advances in RNA m⁶A biology by focusing on writers, readers, and erasers of m⁶A modification, and describe the development of high-throughput methods for RNA m⁶A mapping. We further discuss the important roles of m⁶A modifiers in acute myeloid leukemia, and highlight the identification of potential inhibitors for AML treatment by targeting of m⁶A modifiers. Overall, this review provides a comprehensive summary of RNA m⁶A biology in acute myeloid leukemia.

Regulated cell death (RCD) is essential for maintaining cell homeostasis and preventing diseases. Besides classical apoptosis, several novel nonapoptotic forms of RCD including NETosis, pyroptosis, ferroptosis, and cuproptosis have been reported and are increasingly being implicated in various cancers and inflammation. Disulfiram (DSF), an aldehyde dehydrogenase inhibitor, has been used clinically for decades as an anti-alcoholic drug. New studies have shown that DSF possesses potent anti-inflammatory and anti-cancer effects by regulating these new types of RCD. Here, we summarize the mechanisms and discuss the potential application of DSF in the treatment of cancers and inflammatory diseases.