Acute Myelogenous Leukemia

P1, N=12, Recruiting, City of Hope Medical Center | Suspended --> Recruiting

UBC9 silencing resulted in viability decrease, apoptosis and lipid peroxidation promotion, Fe2+ upregulation, and GPX4, SLC7A11, and PPARα downregulation in THP-1 cells, which were all counteracted by pirinixic acid. UBC9 silencing-induced PPARα deSUMOylation induces suppression of AML cell growth by ferroptosis.

Mutation-specific NPM1 IHC is a valuable tool for a rapid assessment of residual morphologic and molecular disease in mid- and postinduction NPM1mut AML.

The effect of GDF11 on chemotherapy sensitivity was investigated in HL60 cells treated with 10 μM daunorubicin (DNR)...In addition, CTSS activated the extracellular signal-regulated kinase 1 and 2 signaling pathway and inhibited endoplasmic reticulum stress in AML cells. In conclusion, GDF11 inhibited the growth and increased chemosensitivity through inhibiting CTSS expression in AML cells, providing potential therapeutic targets for AML treatment.

Treatment with low-dose Len in transfusion-independent del(5q) MDS reduced the mutational burden of most genes and did not promote the expansion of preexisting clones or AML progression, especially TP53-mutated clones. Early administration of Len in del(5q) MDS patients without TD may be an effective therapeutic approach with a manageable safety profile regarding clonal evolution.

Due to resource constraints, all-trans retinoic acid-based therapy was unavailable, and induction chemotherapy was administered, with a fatal outcome after one week. This case highlights gingival hypertrophy as an atypical early presentation and the impact of delayed diagnosis and limited access to essential therapy.

Collectively, our work repositions MO-IPS from a cytotoxic MYC-PRMT inhibitor to a multifaceted immunometabolic therapeutic. At optimized lower doses, it orchestrates a coordinated disruption of cancer metabolic vulnerabilities and actively augments anti-tumor immunity, presenting a refined and highly promising combinatorial strategy for AML.

More harmonized assay workflows, standardized reporting of results, prospectively validated thresholds, and demonstration of the clinical value of TIM-3 beyond known MRD and genetic risk models are needed to enable the translation of TIM-3 into routine AML laboratory practices. Therefore, TIM-3 should currently be regarded as a promising adjunctive AML biomarker; however, it is not recommended for standalone routine clinical decision-making outside clinical trials.

Overexpression of anti-apoptotic protein BCL-2 and hypermethylation are hallmarks of acute lymphoblastic leukemia (ALL) and can be pharmacologically addressed by venetoclax (VEN) and hypomethylating agents (HMA) such as azacytidine (AZA) or decitabine (DEC). AZA-induced metabolic suppression as well as overall anti-leukemic activity alone and in combination with VEN was generally weaker compared to DEC. Altogether, we herein demonstrate that combined VEN and HMA application acts synergistically and significantly reduces the leukemic burden in ALL cell lines via impairment of tumor cell metabolism and mitochondrial function.

PRAME immunohistochemistry with a cut-off of ≥ 3+ is useful for differentiating AM from AMN. However, false positivity and negativity of PRAME expression must be considered.

Here, we found that multiple lipid metabolism processes are aberrantly activated in Ara-C resistant AML cells, accompanied by upregulation of JAK-STAT3 signaling and key lipid metabolic regulators, notably SREBP1 and CPT2...Our findings highlight the critical role of STAT3-driven lipid metabolism reprogramming in chemoresistance. Furthermore, W1307 emerges as a promising therapeutic candidate to overcome chemoresistance in leukemia treatment.

This optimized model demonstrated significant improvement, reducing the difference in the description of exposure for the microdose study from 5- to 1-fold, without compromising the description at therapeutic doses. This modified model has a wider range of applicability across doses and could support the extrapolation of microdose study results to therapeutic doses in future research.