Here, we show that small extracellular vesicles (sEVs) derived from leukemic cells resistant to decitabine (DAC-R), a commonly used HMA, promote vascular permeability by downregulating tight junction proteins, including ZO-1, occludin, and claudin5, in endothelial cell monolayers...Functionally, vascular remodeling driven by fucosylated sEVs promotes leukemic dissemination, suggesting that disruption of vascular homeostasis represents an additional layer of therapeutic resistance. These findings define a TWIST1-FUT4-LeX-ICAM3 axis and highlight glycosylation as a critical mediator of vascular microenvironment remodeling in MDS/AML.

P1/2, N=20, Recruiting, Erasmus Medical Center | Not yet recruiting --> Recruiting

Results from the Japanese population enrolled in AGILE are aligned with those of the overall study. The efficacy of ivosidenib plus azacitidine in Japanese mIDH1 AML patients enrolled in AGILE who were ineligible for intensive chemotherapy appears to be consistent with the overall study population.

All patients achieved complete remission (CR) after 1-2 courses of induction therapy, followed by consolidation with high-dose cytarabine (HiDAC). MT with either decitabine or chemotherapy can improve outcomes of AML patients in this real-world cohort. Decitabine maintenance exhibits better tolerability compared with chemotherapy and enhances survival in specific patient subgroups.

P2, N=126, Not yet recruiting, National Cancer Institute (NCI)

The early use of VEN-AZA appears to be effective and well tolerated in AML patients with molecular relapse after allo-HSCT, particularly in those carrying CBFβ::MYH11 fusion gene or NPM1 mutation.

Guadecitabine, a hypomethylating agent (HMA), has shown promising clinical activity when combined with carboplatin in preclinical models. Methylome changes in peripheral blood mononuclear cell (PBMCs) from small cell lung cancer (SCLC) patients treated with an epigenetic therapy revealed global hypomethylation and altered cancer signaling processes associated with tumor progression, immune response, therapy resistance and significant change in the proportion of immune cells. Integrating blood-based methylation biomarkers into clinical trials of epigenetic therapy and methylomic analysis of PBMCs provides direct monitoring of treatment effects in cancer patients, which may improve patient selection and enable real-time response assessment in patients receiving hypomethylating agents.

This phenomenon is reversible with the epitranscriptomic compound 5-azacytidine. Consistent with these findings, IP expression is excluded from hypoxic regions in most human NSCLC tumors. Together, these results link tumor hypoxia to a state of "immunogenic dormancy" and identify stress granules as a previously unrecognized mechanism of immune escape.

For instance, the azacytidine/venetoclax/gilteritinib triplet as first-line is reported to induce a complete remission rate with and without incomplete recovery (CR/CRi) of 96%, with 90% of responders achieving minimal residual negativity. Besides regimens containing approved inhibitors, triplets with next-generation inhibitors, including completely orally administered triplet regimens, are also summarized. Their promising results are leading to advanced phase clinical studies by international consortia and collaborative groups, aiming to further refine their clinical management.

RNR inhibition led to increased incorporation of DAC into genomic DNA by reducing the availability of dCTP. These findings nominate the promising combination therapy of DAC and RNR inhibitors as being ripe for further clinical translation.

P2/3, N=230, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Jul 2026 --> Jul 2028 | Trial primary completion date: Jan 2026 --> Jul 2028

P2, N=80, Not yet recruiting, Shirley Ryan AbilityLab