血液科学(英文)最新文献

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.

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.

Adult T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive subtype of non-Hodgkin's lymphoma that differs from pediatric T-LBL and has a worse prognosis. Due to its rarity, little is known about the genetic and molecular characteristics, optimal treatment modalities, and prognostic factors of adult T-LBL. Therefore, we summarized the existing studies to comprehensively discuss the above issues in this review. Genetic mutations of NOTCH1/FBXW7, PTEN, RAS, and KMT2D, together with abnormal activation of signaling pathways, such as the JAK-STAT signaling pathway were described. We also discussed the therapeutic modalities. Once diagnosed, adult T-LBL patients should receive intensive or pediatric acute lymphoblastic leukemia regimen and central nervous system prophylaxis as soon as possible, and cranial radiation-free protocols are appropriate. Mediastinal radiotherapy improves clinical outcomes, but adverse events are of concern. Hematopoietic stem cell transplantation may be considered for adult T-LBL patients with high-risk factors or those with relapsed/refractory disease. Besides, several novel prognostic models have been constructed, such as the 5-miRNAs-based classifier, 11-gene-based classifier, and 4-CpG-based classifier, which have presented significant prognostic value in adult T-LBL.

The maintenance of the mammalian blood system depends on hematopoietic stem cells (HSCs), which are a rare class of adult stem cells with self-renewal and multilineage differentiation capacities. The homeostasis of hematopoietic stem cells is finely tuned by a variety of endogenous and exogenous regulatory factors, and disrupted balance will lead to hematological diseases including leukemia and anemia. Recently, emerging studies have illustrated the cellular and molecular mechanisms underlying the regulation of HSC homeostasis. Particularly, the rapid development of second-generation sequencing technologies has uncovered that many small noncoding RNAs (ncRNAs) are highly expressed in HSCs, including snoRNAs, miRNAs, tsRNAs, circular RNAs, etc. In this study, we will summarize the essential roles and regulatory mechanisms of these small ncRNAs in maintaining HSC homeostasis. Overall, this review provides up-to-date information in the regulation of HSC homeostasis by small ncRNAs, which sheds light into the development of therapeutic strategies against hematopoietic malignancies.

Purpureocillium lilacinum (P lilacinum) is a rare pathogenic fungus, which mainly involves immunocompromised individuals. Here, we report a case of complicated multiple-organ infections involving skin, lungs, and spleen in a 63-year-old female with Evans' syndrome after 9 months of glucocorticoid treatment. Microbial examinations of skin biopsy and blood samples revealed P lilacinum infections. Posaconazole was effective in this patient. During anti-fungi treatment, she developed varicella-zoster virus infection and was diagnosed through next-generation sequencing examination. In conclusion, P lilacinum may affect different organ systems and is susceptible to posaconazole treatment. The molecular-based methods like microbial cell-free DNA sequencing could provide accurate and timely identification of a wide range of infections.

Warfarin is a commonly used oral anticoagulant. Patients with artificial valve replacement, atrial fibrillation, pulmonary embolism, deep vein thrombosis, and other diseases require long-term anticoagulant oral treatment with warfarin. As warfarin exhibits prompt action with long maintenance time, it has become a key drug for the treatment of patients at risk of developing thrombosis or thromboembolism. Warfarin is a bican coumarin anticoagulant, that exhibits competitive action against vitamin K as its mechanism of action, thereby inhibiting the synthesis of coagulation factors-predominantly the vitamin K-dependent coagulation factors II, VII, IX, and X-in hepatocytes. Long-term warfarin is known to significantly increase the risk of organ bleeding in some patients, while some patients may need to reverse the anticoagulation effect. For instance, patients scheduled for emergency or invasive surgery may require rapid anticoagulation reversal. During such medical circumstances, fresh frozen plasma (FFP) is clinically used for the reversal of excess warfarin-associated anticoagulation, as it contains all the coagulation factors that can alleviate the abnormal blood anticoagulation status in such patients. Accordingly, this article aims to perform an in-depth review of relevant literature on the reversal of warfarin with FFP, and insightful deliberation of the application and efficacy of this clinical intervention.