So far, pre-clinical and clinical studies showed promising results when Bcl-2 (Genasense), Mcl-1 (ISIS2048), STAT3 (ISIS345794) and IRF4 (ION251) were targeted using ASOs-based formulations. The relevant genetic targets in ASOs-based MM therapies were described, and the research results obtained in the studies conducted so far were analyzed, with a focus on the ASOs formulations that were already included in clinical trials. In the end, current challenges, and future perspectives of antisense therapy for MM were also discussed.

P1, N=23, Completed, Ionis Pharmaceuticals, Inc. | Active, not recruiting --> Completed | Trial completion date: Jan 2024 --> Sep 2024 | Trial primary completion date: Jan 2024 --> Sep 2024

P1, N=23, Active, not recruiting, Ionis Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting | N=80 --> 23

In vitro experiments demonstrated that the overexpression of IRF4 inhibited the proliferation and migration capacity of HCC cells by restricting the JAK2/STAT3 signalling pathway and epithelial-mesenchymal transition. Overall, our study identified a novel IRF4 risk score that could serve as a robust prognostic biomarker and provide therapeutic benefits for immunotherapy in HCC patients, which may be helpful for clinical decision-making for HCC patients.

Hence, the present work demonstrated that alvocidib has therapeutic efficacy against ATL and partially elucidated its mode of action. It also showed that alvocidib is promising for the clinical treatment of ATL and perhaps other malignancies and neoplasms as well.

Taken together, this cell line deals with two conflicting oncogenic drivers, namely, JAK2-STAT3 signaling and EBV infection, but is sensitive to switch after cytokine stimulation. Thus, AM-HLH represents a unique cell line model to study the pathogenic roles of STAT3 and EBV and their therapeutic implications in HL.

In support of our experimental observations, gene network modelling of MM suggests that bromodomain inhibition is exerted primarily through MYC and not IRF4. These findings suggest that despite the autofeedback positive regulatory loop between IRF4 and MYC, bromodomain inhibitors are not effective at targeting IRF4 in MM and that novel therapeutic strategies should focus on the direct inhibition or degradation of IRF4.

FNABC with CBs is an acceptable alternative to biopsy for providing a complete diagnosis of DLBCL as per the current WHO classification.

Elevenostat demonstrated nanomolar ex vivo activity in 34 MM patient specimens and synergistic activity when combined with bortezomib. Collectively, our data indicate that HDAC11 is an emerging therapeutic vulnerability in MM by targeting an essential pathway in PC biology.

Furthermore, treatment with an EZH2-inhibitor reproduced the IMiD-mediated effects in HTLV-1-infected cells and multiple myeloma cells. These findings strongly suggest that a reduction of EZH2 expression is involved in the mechanism underlying the antitumor effects of IMiD.

miR-155-5p promoted the proliferation of ALL cells and inhibited their apoptosis by inhibiting the expression of CBL, which otherwise degraded IRF4 protein through ubiquitination, leading to inhibited CDK6 expression. Collectively, the results show that miR-155-5p can promote the development of cALL via the regulation on CBL-mediated IRF4/CDK6 axis.

Based on the gross distribution and histological and immunohistochemistry features, a diagnosis of disseminated histiocytic sarcoma was made. To the best of our knowledge, this is the first record of disseminated histiocytic sarcoma in a captive Bengal tiger.