Leukemia research最新文献

Introduction background

This study evaluated the impact of adipose tissue indices on prognosis of HL.

Methods

Fifty-five patients with newly diagnosed Hodgkin Lymphoma were evaluated retrospectively for association with adipose tissue indices (total abdominal tissue volume, radiodensity, subcutaneous and visceral adipose tissue SUVmax value and prognostic factors for Hodgkin Lymphoma such as IPS-3, IPS-7, stage, sedimentation, progression free and overall survival.

Results

For IPS-3, SAT SUVmax and TAAT radiodensity were significantly increased in high-risk patients (2and 3) compared to group 0 and 1. For IPS-7, total abdominal adipose volume was significantly decreased in high-risk patients, SAT SUVmax significantly increased in high-risk patients and decreased in low-risk patients. In addition, SAT SUVmax was significantly increased in patients with high sedimentation rate, with B symptoms and who passed away during follow-up. SAT SUVmax showed moderate positive correlation with sedimentation, IPS-3, IPS-7, and stage. In addition, it was observed that TAAT radiodensity and SAT SUVmax were significantly better for determining prognosis than other adipose tissue indices. Roc analysis showed that the diagnostic value of all adipose tissue indices in predicting IPS-3 and IPS-7 prognoses were statistically significant.

Conclusion

SAT SUVmax and TAAT radiodensity were two new and independent markers with diagnostic value in predicting prognosis.

Objective

To explore the involvement of TFEB-mediated autophagy-lysosomal mechanisms in multiple myeloma (MM) during bortezomib treatment.

Methods

MM cells were exposed to bortezomib or subjected to TFEB knockdown. CCK assay was used to assess the cell proliferation. Western blotting and fluorescent staining were conducted to examine autophagy and lysosomes. The TFEB expression pattern was analyzed, and whole transcriptome sequencing was carried out. Additionally, TFEB target genes were predicted using the GTRD(http://gtrd.biouml.org/) website, and pathway analysis was performed.

Results

Bortezomib demonstrated a dose-dependent and time dependent inhibition of cell proliferation. In MM cells treated with bortezomib, LC3B, Beclin-1, TFEB, and Lamp1 exhibited upregulation in a time- and concentration-dependent manner. LysoTracker dye labeling showed an increase in lysosomes in the bortezomib-treated group. Moreover, bortezomib elevated the expression of lysosome-associated factor Lamp1. Bortezomib promoted the nuclear translocation of TFEB, leading to decreased cytoplasmic TFEB and increased nuclear TFEB. TFEB gene silencing reversed bortezomib's inhibitory effect on MM cell lines, significantly reducing autophagosome expression and lysosome numbers. Furthermore, bioinformatic analysis identified the MAPK pathway as a potential downstream target of TFEB.

Conclusion

Bortezomib effectively inhibits MM cell proliferation and induces autophagy, partly through TFEB-mediated mechanisms, with potential involvement of the MAPK pathway.

Inherited bone marrow failure syndromes and germline predisposition syndromes (IBMFS/GPS) are associated with increased risk for hematologic malignancies, particularly myeloid neoplasms, such as myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). The diagnosis of MDS in these syndromes poses difficulty due to frequent bone marrow hypocellularity and the presence of some degree of dysplastic features related to the underlying germline defect causing abnormal maturation of one or more cell lines. Yet, the diagnosis of MDS is usually associated with a worse outcome in several IBMFS/GPS. Criteria for the diagnosis of MDS in IBMFS/GPS have not been standardized with some authors suggesting a mixture of morphologic, cytogenetic, and genetic criteria. This review highlights these challenges and suggests a more standardized approach to nomenclature and diagnostic criteria.

Patients with acute myeloid leukemia (AML) may experience extramedullary involvement when disease is present outside of the blood and bone marrow. In particular, the presence of central nervous system (CNS) involvement has traditionally been thought of as a poor prognostic factor. In the presently available literature, there is a paucity of conclusive data surrounding CNS AML given its rarity and lack of unified screening practices. Thus, we performed a systematic review and meta-analysis in order to more definitively characterize survival outcomes in this patient population. In this meta-analysis, we evaluated survival outcomes and response rates from clinical studies on patients with AML stratified by the presence of CNS involvement. Twelve studies were included in the meta-analysis with a resulting hazard ratio (HR) for overall survival (OS) of 1.34 with a 95 % CI of 1.14 to 1.58. These findings suggest that CNS involvement in adult patients with AML is associated with an increased hazard of mortality compared to those patients without CNS involvement. As such, CNS involvement should be viewed as negative prognostic marker, and attention should be made to ensure prompt identification and treatment of patients who experience this complication.

Background

Circular RNAs (circRNAs) are associated with development and progression of multiple myeloma (MM). However, the role and mechanism of circ_0005615 in MM have not been elucidated.

Methods

Circ_0005615 was determined by GEO database. quantitative RT-PCR was performed to confirm the expression of circ_0005615 in peripheral blood of MM patients and MM cells. The roles of circ_0005615 in MM were analyzed using CCK8, transwell invasion, cell apoptosis and tumor xenograft experiments. Bioinformatics tools, RIP and RNA pull down assays were conducted to explore the downstream of circ_0005615. Furthermore, the mechanism was investigated by quantitative RT-PCR, western blot, dot blot and meRIP-PCR assays.

Results

Circ_0005615 was upregulated in MM. Overexpression of circ_0005615 promoted cell viability and invasion, and suppressed apoptosis in vitro, which were opposite when circ_0005615 was knockdowned. Mechanistically, EIF4A3, a RNA-binding protein (RBP), could directly bind to circ_0005615 and ALKBH5, where ALKBH5 could directly combine with MAP3K4, forming a circ_0005615- EIF4A3-ALKBH5-MAP3K4 module. Furthermore, circ_0005615 overexpression increased m6A methylation of MAP3K4 by inhibiting ALKBH5, leading to decreased MAP3K4. Further functional experiments indicated that ALKBH5 overexpression weakened the promoting roles of circ_0005615 overexpression in MAP3K4 m6A methylation and tumor progression in MM. The above functions and mechanism were also verified in vivo.

Conclusions

Elevated circ_0005615 decreased MAP3K4 mediated by ALKBH5 through interacting with EIF4A3, thereby accelerating MM progression. Circ_0005615 might be a promising biomarker and target of MM.

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the sole curative option for many hematological malignancies and other diseases. Nevertheless, its application is limited due to the risk of life-threatening complications, mainly graft-versus-host disease (GVHD). Currently, in clinical practice, the risk of developing GVHD is estimated for every patient based on factors related to the donor and the host. In our prospective, observational study, we analyzed serum from 38 patients undergoing allo-HCT at our institution. We compared the metabolic profiles of patients who developed acute GVHD (aGVHD) with those without such complication by identification and comparison of metabolites masses on the XCMS platform. We observed that patients diagnosed with aGVHD had different metabolic profiles compared to the remaining patients and this alteration was noticeable already 7 days before the procedure. We identified dysregulated metabolites involved in bile acid transformation and cholesterol synthesis. Our study of the untargeted metabolome in allo-HCT recipients has revealed a potential link between lipid metabolism, specifically involving bile acid transformation and cholesterol synthesis, and the development of aGVHD. This finding might be an important indication for future research focused on understanding GVHD development, discovering prediction models, and investigating possible prophylactic interventions.