Functional analyses demonstrated that altered ABCB6 expression did not significantly affect cell proliferation or apoptosis; however, targeted knockdown of ABCB6 markedly restored the sensitivity of K562/A02 cells to adriamycin (ADR) and cytosine arabinoside (Ara-C). Mechanistic studies revealed that ABCB6 contributes to ADR efflux from leukemia cells, thereby reducing intracellular drug accumulation and weakening its cytotoxic activity. Together, these findings establish ABCB6 as a previously unrecognized efflux transporter that contributes to MDR in leukemia and highlight ABCB6 as a potential therapeutic target for overcoming MDR.

Concurrently, it suppresses Polo-like kinase 1 (PLK1) expression, thereby inducing G2/M cell cycle arrest and activating apoptotic pathways. Collectively, our findings identify NTZ as a potent anti-tumor agent and chemosensitizer that restores Ara-C responsiveness, offering a promising combinatorial strategy for the treatment of refractory AML.

Traditional IT agents such as methotrexate or cytarabine were generally associated with modest survival outcomes, whereas more recent studies evaluating IT pemetrexed and molecularly guided regimens reported longer survival in selected cohorts, particularly in EGFR-mutant NSCLC-LM. Ommaya reservoir-based delivery may offer practical advantages for repeated treatment and CSF monitoring in appropriately selected patients, with acceptable toxicity and manageable device-related risks. Emerging data on pemetrexed-based intrathecal regimens and other molecularly informed approaches suggest potential benefit in selected subgroups, but prospective, multicenter, mutation-stratified studies are needed to refine patient selection, optimize dosing strategies, and define the comparative role of different intrathecal delivery routes.

We identify the host nucleotide excision repair component, XPA, and the repair enzyme, polymerase kappa, as each being necessary for mutant virus ganciclovir resistance and polymerase kappa as being required for the mutant's cidofovir resistance, demonstrating a role for host DNA repair machinery in a mechanism of antiviral resistance. This mechanism is relevant to at least one other antiviral drug and may apply to other antiviral and anticancer agents. The study also showcases the participation of host DNA repair machinery during human cytomegalovirus DNA synthesis.

These findings identify BMP and ERK signaling as context-dependent regulators of Ara-C response in AML and demonstrate that stromal interactions evolve during resistance acquisition. Targeting BMP and ERK pathways, together with modulators of DNA repair or drug efflux, may provide therapeutic strategies to reduce relapse and improve AML outcomes.

Here we detail two patient cases illustrating the real-world use of quizartinib in combination with anthracycline and cytarabine-based chemotherapy and maintenance monotherapy for the management of FLT3-ITD+ AML. These cases highlight the practical recommendations on management of quizartinib-based chemotherapy in accordance with the Food and Drug Administration (FDA)-mandated REMS requirements. Adopting these strategies to optimize the safe treatment of FLT3-ITD+ AML with quizartinib may ultimately improve patient outcomes in this highly challenging malignancy.

Furthermore, HELLS deficiency enhanced myeloid differentiation and apoptosis in HL-60 cells when treated with chemotherapy drugs, including 5-azacytidine, cytarabine, and doxorubicin. Ex vivo validation in AML patient-derived LSPCs demonstrated that HELLS deficiency reduces leukemic marker burden (CD123 and TIM-3) and increases apoptosis. Overall, we show HELLS upregulation drives leukemogenesis with poor outcomes, highlighting its potential as a prognostic marker and therapeutic target in AML.

This scoring system was then applied to the transcriptomic data from a cohort of 838 newly diagnosed patients treated on Alliance/CALGB protocols, who were similarly treated with intensive cytarabine/daunorubicin-based chemotherapy on the CALGB/Alliance for the Clinical Trials in Oncology protocol. We also noted a strong association of FLT3-ITD, RUNX1 and TP53 mutations with high LAM scores. Applying the LAM score to the current European Leukemia Network risk group criteria, independent prognostic implications and a refined prognostic significance of each subgroup were provided, indicating the value of including immune microenvironment data into AML risk stratification.

This study unveils a novel FTO/m6A/TPM1 axis that coordinately governs AML cell growth, chemosensitivity, and macrophage polarization, highlighting it as a promising therapeutic target.

Core-binding factor (CBF) acute myeloid leukemia (AML) with t(8;21)(q22;q22)/RUNX1::RUNX1T1 is typically considered as a favorable-risk AML in the context of cytarabine-based intensive chemotherapy...Here, we report the case of a young patient diagnosed with CBF-AML and RUNX1::RUNX1T1 fusion gene, carrying a rare and complex three-way t(8;11;21)(q22;q13;q22) translocation, with mutated KIT, ASXL1 and TET2 genes, transforming into an aggressive and multi-refractory mediastinal myeloid sarcoma. This case illustrates that this scarcely reported variant might negatively impact the favorable prognosis of CBF-AML.

Low-dose Andro strengthens Ara-C- and VCR-driven cytotoxic programs and provides a quantitative rationale for Andro-based combination strategies in plasma cell neoplasms and related hematologic malignancies.

An integrated management strategy was instituted, comprising early empiric coverage for Pneumocystis jirovecii pneumonia, targeted therapy with ganciclovir and levofloxacin, and adjunctive immunomodulation using intravenous immunoglobulin and corticosteroids. This case challenges the conventional time-based risk paradigm and supports immune-guided surveillance. It underscores the transformative role of mNGS in diagnosing complex infections in immunocompromised patients and advocates for a management paradigm that concurrently addresses pathogen eradication and host immune dysfunction.