ETV6-rearranged acute lymphoblastic leukemia (ALL) is associated with poor prognosis in adults. Previously, a super-enhancer (SE) located within the ETV6 intragenic region (ETV6-SE) was identified in a rare fusion gene, ETV6::ACSL6, but further work is needed to determine whether ETV6-SE is broadly present in ALL and how ETV6 rearrangements impact the SE function. Here, we demonstrated that ETV6 functions as a regulatory element via ETV6-SE in ALL, with CDKN1B as a key target. CRISPR interference and knockout experiments revealed the core enhancer region within ETV6-SE responsible for CDKN1B regulation. ETV6 rearrangements disrupted ETV6-SE and impaired long-range chromatin interaction with the CDKN1B locus, leading to its downregulation that in turn activated the NF-κB pathway and increased expression of anti-apoptotic proteins BCL-2/BCL-XL. In patient-derived xenograft (PDX) models, pharmacological inhibition of BCL-2/BCL-XL using venetoclax or navitoclax showed additive effects when combined with dexamethasone. Collectively, these findings establish the ETV6-SE-CDKN1B regulatory axis as a mechanism contributing to treatment resistance in ETV6-rearranged ALL.
Wenqian Xu, Xiaofang Ma, Xue Sun et al.· Cancer Research· 0 citations
RATIONALE AND OBJECTIVES
This study aimed to explore the diagnostic value of super-resolution ultrasound (SRUS) in differentiating benign from malignant renal solid tumors by assessing microvascular characteristics, and to find if combining SRUS with conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) potential enhances diagnostic utility.
MATERIALS AND METHODS
This prospective study included 114 pathologically confirmed renal lesions. All patients underwent conventional US, CEUS, and SRUS. We analyzed qualitative and quantitative parameters of CEUS and SRUS, screened significant parameters by univariate analysis, and used a comprehensive diagnostic score method for exploratory receiver operating characteristic (ROC) analysis to construct multiparametric diagnostic panels. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve area under the curve (AUC).
RESULTS
Among 114 masses (88 malignant, 26 benign), malignant lesions exhibited more tortuous vessels and higher microvascular image complexity (p < 0.05). After normalization, microvascular density (MVD) and microbubble velocity showed high spatial heterogeneity in malignancies. CEUS excelled in macroscopic perfusion (AUC=0.842), while SRUS provided incremental microscopic structural information (AUC=0.678); both outperformed conventional US (AUC=0.638). Crucially, the combination of SRUS and CEUS demonstrated improved diagnostic performance (AUC=0.871) in this cohort, suggesting potential complementary value over either modality alone.
CONCLUSION
SRUS non-invasively reveals unique microvascular architecture and heterogeneity in renal malignancies. The combined SRUS-CEUS approach shows promise for improving differential diagnostic accuracy. These results are exploratory and provide preliminary evidence for the potential value of SRUS in renal tumor diagnosis. Key limitations include a relatively small proportion of benign tumors, lacking correction for multiple comparisons, and lack of integration with CEUS time-intensity curve quantitative parameters.
Lu Zhang, Jie Tian, Yilai Chen et al.· Academic Radiology· 0 citations