血液科学(英文)最新文献

[This corrects the article DOI: 10.1097/BS9.0000000000000019.].

[This corrects the article DOI: 10.1097/BS9.0000000000000049.].

[This corrects the article DOI: 10.1097/BS9.0000000000000039.].

[This corrects the article DOI: 10.1097/BS9.0000000000000093.].

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy often associated with poor outcomes. To identify high-risk factors and potential actionable targets for T-ALL, we perform integrated genomic and transcriptomic analyses on samples from 165 Chinese pediatric and adult T-ALL patients, of whom 85% have outcome information. The genomic mutation landscape of this Chinese cohort is very similar to the Western cohort published previously, except that the rate of NOTCH1 mutations is significant lower in the Chinese T-ALL patients. Among 47 recurrently mutated genes in 7 functional categories, we identify RAS pathway and PTEN mutations as poor survival factors for non-TAL and TAL subtypes, respectively. Mutations in the PI3K pathway are mutually exclusive with mutations in the RAS and NOTCH1 pathways as well as transcription factors. Further analysis demonstrates that approximately 43% of the high-risk patients harbor at least one potential actionable alteration identified in this study, and T-ALLs with RAS pathway mutations are hypersensitive to MEKi in vitro and in vivo. Thus, our integrated genomic analyses not only systematically identify high-risk factors but suggest that these high-risk factors are promising targets for T-ALL therapies.

The China's top 10 hematological advances in 2021 was announced at the 2^nd Annual Meeting of Chinese Alliance for Societies of Hematology on January 16, 2022.

Fanconi anemia (FA), an X-linked genetic or autosomal recessive disease, exhibits complicated pathogenesis. Previously, we detected the mutated Dynein Axonemal Heavy Chain 2 (DNAH2) gene in 2 FA cases. Herein, we further investigated the potential association between DNAH2 and the homologous recombination repair pathway of FA. The assays of homologous recombination repair, mitomycin C (MMC) sensitivity, immunofluorescence, and ubiquitination modification were performed in U2OS and DR-U2OS cell lines. In MMC-treated U2OS cells, the downregulation of the DNAH2 gene increased the sensitivity of cells to DNA inter-strand crosslinks. We also observed the reduced enrichment of FANCD2 protein to DNA damage sites. Furthermore, the ubiquitination modification level of FANCD2 was influenced by the deficiency of DNAH2. Thus, our results suggest that DNAH2 may modulate the cell homologous recombination repair partially by increasing the ubiquitination and the enrichment to DNA damage sites of FANCD2. DNAH2 may act as a novel co-pathogenic gene of FA patients.

Interleukin 34 (IL-34) is a cytokine that shares the receptor with colony-stimulating factor 1 (CSF-1). IL-34 is involved in a broad range of pathologic processes including cancer. We previously demonstrated that IL-34 promoted the proliferation and colony formation of human acute monocytic leukemia (AMoL) cells. However, the mechanism has not been elucidated. Here, by analyzing the gene profiles of Molm13 and THP1 cells overexpressing IL-34 (Molm13-IL-34 and THP1-IL-34), upregulation of the DNA damage-inducible transcript 4 (DDIT4) was detected in both series. Knockdown of DDIT4 effectively inhibited the proliferation, promoted apoptosis and colony formation in Molm13-IL-34 and THP1-IL-34 cells. Our results suggest that DDIT4 mediates the proliferation-promotive effect of IL-34 whereas does not mediate the promotive effect of IL-34 on colony formation in AMoL cells.

GSDME contains a pore-forming domain at its N-terminal region to execute pyroptosis. Our previous study has reported that forced expression of Gsdme impairs the reconstitution capacity of hematopoietic stem cells (HSCs). While, how GSDME-mediated pyroptosis regulates HSCs remains unknown. Here, we show that hematopoietic stem and progenitor cells are capable to undergo pyroptosis in response to cisplatin treatment and GSDME is one of the genes mediating such process. Gsdme ^-/- mice revealed no difference in the steady state of blood system while Gsdme ^-/- HSCs exhibited compromised reconstitution capacity due to increased apoptosis. Briefly, this study reveals that GSDME modulates HSC function by coordinating pyroptosis and apoptosis.