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.

He initially responded to ganciclovir, but CMVR recurred five months later, accompanied by new pulmonary nodules...mNGS and PET-CT are critical tools in the diagnostic workup, but definitive diagnosis relies on histopathological confirmation. Early recognition of such presentations can prevent delays in diagnosing aggressive lymphomas.

The first-day CD34⁺ cell count provides a robust, real-time tool for guiding apheresis. HD-Ara-C-based mobilisation should be considered the preferred regimen for fit patients, with steady-state mobilisation as an alternative for selected cases.

Although the European LeukemiaNet (ELN) classifications (2017 and 2022) for AML have been used to stratify outcomes for patients receiving intensive chemotherapy, their application to patients receiving less intensive therapy, such as azacitidine plus venetoclax, has been less satisfactory. Overall, these data support the importance of molecular subclassification in defining treatment outcomes to venetoclax-based therapies. These trials were registered at www.clinicaltrials.gov as #NCT02287233 and #NCT03069352.

Here, we report that elevated bone-marrow leptin and blast-cell leptin-receptor (LEPR) levels strongly associate with poor cytarabine (Ara-C) clearance and reduced survival in newly diagnosed AML patients...Leptin up-regulates LEPR and triggers JAK2/STAT3 signaling that boosts mitochondrial complex Ⅰ activity, oxidative phosphorylation, and mitochondrial reactive oxygen species (mtROS); the resulting mtROS surge activates a compensatory antioxidant program that shields blasts from drug-induced oxidative damage. These data identify an adipokine-driven metabolic circuit governing AML chemoresistance and reveal LEPR blockade as a tractable strategy to improve outcomes, underscoring adipose-tumor crosstalk as a general therapeutic vulnerability.

Summarizing, the leukemic blasts and AML-MSC in the BM microenvironment interact differentially in cell-cell contact compared to only soluble factors. Further, our study has provided innovative leads that PD-MSC-CM effectively abrogates leukemia tumor growth, enhances chemosensitivity and can be developed further as an immunomodulatory novel "off-the-shelf" therapeutic agent for leukemia.

Mechanistically, we demonstrate that HS6ST1 depletion in AML cells reduces TGF-β1-mediated signaling, which diminishes cell survival upon cytarabine treatment. Together, our data show that HS6ST1 promotes AML cell chemotherapy resistance by supporting TGF-β1 signaling.

Furthermore, the histopathological alterations induced by Cyt were markedly ameliorated by both antioxidants. These results suggest that Cyt-induced neuronal degeneration is driven by oxidative stress and apoptosis, processes that can be mitigated by morin and propolis supplementation.

Correspondingly, genetic inhibition of OPTN suppressed mitophagy, disrupted mitochondrial homeostasis, and sensitized cells to cytarabine (Ara-C), ultimately potentiating its antileukemic efficacy in a cell-derived xenograft (CDX) model. Collectively, these findings indicate that OPTN-mediated mitophagy is an oncogenic driver in NPM1-mutated AML and that, targeted inhibition of this process is a promising strategy for overcoming chemoresistance, particularly in combination with conventional chemotherapy.

Consequently, this FOSL2-deficient state profoundly sensitizes AML cells to conventional chemotherapies, including doxorubicin and cytarabine, as well as ER stress-inducing agents. Collectively, these findings establish that FOSL2 orchestrates a key proteostatic vulnerability. Targeting the FOSL2-ERAD axis represents a compelling therapeutic strategy to dismantle chemoresistance and improve patient outcomes in AML.

We show that approved drugs inhibiting IMPDH-mycophenolic acid and ribavirin-imbalance deoxyribonucleoside triphosphate pools and increase ara-C efficacy in SAMHD1-proficient, but not deficient, leukaemic cells. Altogether, we provide insight into SAMHD1 regulation in leukaemic cells and show how this process can be exploited by approved drugs to improve ara-C therapy.

P2/3, N=72, Not yet recruiting, Symbio Pharmaceuticals Ltd.