Leukemia

All three tested derivatives demonstrated moderate to strong binding to bovine serum albumin (BSA), with preferential occupation of subdomain IIA (site I), as supported both experimentally and through docking studies. The interaction study of these compounds with DNA indicated their ability to interact with ct-DNA through the minor groove.

Beyond IL-1 release, NLRP3 may interface with cellular stress responses and pyroptosis, thereby influencing both AML cells and their microenvironment through multiple mechanisms. Inflammasome signaling may act as a driver of therapy resistance while also representing a promising therapeutic target.

Intact pRBCs strongly inhibit megakaryocytic differentiation and disrupt PLP function through transcriptional dysregulation and inflammatory activation, whereas under our experimental conditions, RBC-EVs exert milder modulatory effects. These findings highlight defective platelet production as a novel mechanism contributing to malaria-associated thrombocytopenia.

Ile and Val are glycogenic branched-chain amino acids (BCAAs) that regulate fundamental cell processes by affecting mTOR activation through BCAA metabolism. In conclusion, RPL5 depletion-induced ribosomal stress disrupted stemness maintenance by affecting BCAA metabolism in AML, specifically inhibiting the PI3K-Akt-mTOR signaling pathway, which resulted in LSC eradication.

In conclusion, FLT3-ITD clonal origin demonstrated significant impact on the outcome of AML. Acquired 13q UPD drives clonal evolution and disease progression in the DNMT3A/NPM1-origin subgroup, highlighting its potential as a therapeutic target.

P=N/A, N=300, Not yet recruiting, Colorado State University

P2, N=180, Not yet recruiting, University of Nebraska

P1/2, N=292, Active, not recruiting, ImCheck Therapeutics | Trial completion date: Dec 2025 --> Oct 2026 | Trial primary completion date: Sep 2025 --> Oct 2026

P2, N=47, Recruiting, Institute of Hematology & Blood Diseases Hospital, China | Not yet recruiting --> Recruiting

Immunomodulatory drugs (IMiDs) like lenalidomide and pomalidomide degrade IKZF1/3 and are combined with other therapies to treat hematologic malignancies, including multiple myeloma and non-Hodgkin lymphoma. Molecular docking studies suggested that DIX-01 may form stable ternary complexes with CRBN-IKZF1 and CRBN-GSPT1, providing a structural basis for its dual-target degradation activity. Furthermore, DIX-01 significantly inhibited tumor growth in a zebrafish xenograft model transplanted with human acute myeloid leukemia cells (MV4-11), supporting its potential as a therapeutic agent for hematologic malignancies.

Given the critical importance of CD22 targeting, this experience serves as a foundation for new approaches targeting CD22 while providing ongoing support for dual-targeting approaches and insights into toxicity mitigation. NCT02315612.

Translocations occurred in 11 (61.1%) PCL patients; IGH::CCND1 and IGH::MYC were more frequent in PCL compared to MM (22% vs. 14%, p = NS, and 11% vs. 1%, p < 0.05). Druggable aberrations in BRAF, CCND1, PIK3R1, and RAS may be targeted in biomarker-driven therapeutic clinical trials.