Global, regional, and national burden of acute myeloid leukemia, 1990–2021: a systematic analysis for the global burden of disease study 2021

Biomarker Research, Год журнала: 2024, Номер 12(1)

Опубликована: Сен. 11, 2024

Язык: Английский

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Adamantane-Quinoxalone Hybrids: Precision Chemotypes and Their Molecular Mechanisms in Acute Myeloid Leukemia

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

Acute myeloid leukemia (AML) is an aggressive blood cancer with a poor prognosis, especially when diagnosed late. Around 10–15% of cases involve the specific chromosomal abnormality t(8;21), which drives uncontrolled cell proliferation and contributes to disease onset. Despite advances in AML research treatment protocols, outcomes for t(8;21) remain stagnant, as patients receive standard, nonspecific chemotherapies. This one-size-fits-all approach targets both cancerous healthy cells, leading unwanted toxicity highlighting urgent need targeted therapies. In this study, we present precision chemotype based on quinoxalone-tethered adamantane framework developed via metal- light-free protocol. The compound selectively inhibits induces death by disrupting growth metabolic pathways, demonstrated through bioassays, RNA sequencing, proteomic analysis. Notably, it spares other leukemic solid underscoring its specificity potential therapy AML.

Язык: Английский

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Evolving racial/ethnic disparities in AML survival in the novel therapy era

Blood Advances, Год журнала: 2025, Номер 9(3), С. 533 - 544

Опубликована: Янв. 31, 2025

Язык: Английский

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Prediction model establishment of prognosis factors for acute myeloid leukemia based on the SEER database

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 7, 2025

Acute myeloid leukemia (AML) with t (9;11) (p22; q23) presents as a varied hematological malignancy. The translocation is the most common among 11q23/KMT2A rearrangements in AML. This research aimed to develop nomogram for precise prediction of overall survival (OS) and cancer-specific (CSS) AML translocation. We utilized Surveillance, Epidemiology, End Results (SEER) database identify patients diagnosed from 2000 2021. Prognostic factors this subtype were determined using least absolute shrinkage selection operator (LASSO) regression, which guided creation prognostic nomograms. To evaluate model's discrimination, accuracy, effectiveness, we employed concordance index (C-index), calibration charts, receiver operating characteristic curves (ROC), area under curve (AUC), decision-curve analysis (DCA). was meticulously planned, executed, documented full adherence TRIPOD guidelines. developed key variables including age, race, first primary tumor, chemotherapy. indices (C-indices) 0.704 OS 0.686 CSS. Patients classified into high-risk low-risk groups based on scores, significant differences CSS between these (P < 0.001). study innovative nomograms that combine clinical treatment predict 1-, 3-, 5-year rates

Язык: Английский

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Upregulation of LSP1 in AML cells enhances AML resistance to sorafenib and promotes apoptosis in CD8+ T cells

International Immunopharmacology, Год журнала: 2025, Номер 150, С. 114255 - 114255

Опубликована: Фев. 13, 2025

Язык: Английский

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ITGAM Upregulation in Acute Myeloid Leukemia Leads to Poor Prognosis Associated With Infiltration of Inhibitory Innate Immune Cells

International Journal of Laboratory Hematology, Год журнала: 2025, Номер unknown

Опубликована: Март 7, 2025

Acute myeloid leukemia (AML) is a prevalent and potentially fatal hematologic malignancy with limited improvements in survival rates over the past few decades. ITGAM, encoding CD11b, significant integrin component leukocytes, involved various biological processes. However, its role AML prognosis immune cell infiltration remains poorly understood. This study investigated prognostic significance potential function of ITGAM using comprehensive bioinformatic analyses. expression was markedly upregulated patients, correlating advanced age (> 60 years), French-American-British (FAB) classification subtypes M4 M5, intermediate or poor cytogenetic risk. Gene enrichment analysis revealed that system regulation positively associated neutrophils, immature dendritic cells, macrophages AML. Notably, linked to increased immunosuppressive subsets these innate which may partially explain association poorer prognosis. These findings suggest could serve as valuable biomarker AML, reflecting an adverse enhanced cells.

Язык: Английский

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Multi-omics integration reveals immune hallmarks and biomarkers associated with FLT3 inhibitor sensitivity in FLT3-mutated AML

Blood Science, Год журнала: 2025, Номер 7(2), С. e00227 - e00227

Опубликована: Март 19, 2025

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by poor clinical outcomes, frequently exacerbated mutations in the FMS-like tyrosine kinase 3 (FLT3) gene. Although FLT3 inhibitors (FLT3i) have emerged as promising therapeutic agents, absence of molecular biomarkers to predict FLT3i response remains a critical limitation practice. In this study, we performed comprehensive multi-omics analysis integrating transcriptomic, proteomic, and pharmacogenomic data from Beat AML cohort, Cancer Cell Line Encyclopedia (CCLE), PXD023201 repository elucidate consequences AML. Our revealed significant differences RNA protein expression profiles between FLT3-mutant wild-type cases, with particularly striking association immune suppression. We further evaluated drug sensitivity patients FDA-approved FLT3i, gilteritinib, midostaurin, quizartinib, observed heightened cohorts, accompanied activation immune-related pathways treatment-responsive groups. These findings suggest potential synergy efficacy activation. Through rigorous bioinformatic analysis, identified candidate biomarkers: CD36, SASH1, NIBAN2, associated sensitivity. were consistently upregulated favorable prognostic subgroups demonstrated strong correlations pathways. The identification NIBAN2 predictive offers novel toolset for stratifying prognosis.

Язык: Английский

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New and Effective Inhibitor of Class I HDACs, Eimbinostat, Reduces the Growth of Hematologic Cancer Cells and Triggers Apoptosis

Pharmaceutics, Год журнала: 2025, Номер 17(4), С. 416 - 416

Опубликована: Март 25, 2025

Background: Histone deacetylases (HDACs) are critical epigenetic modulators involved in regulating various molecular mechanisms essential for cell development and growth. Alterations HDAC activity have been linked to the progression of numerous cancers, including lymphoma. Over past decade, FDA has approved several inhibitors lymphoma treatment, leading heightened interest this emerging class drugs. Methods: In our research, we developed a novel inhibitor that exhibits high selectivity I HDACs. Results: Our vitro findings indicate treating lymphoma/leukemia cells with results marked suppression growth promotes apoptosis, while leaving cycle unaffected. Conclusions: We propose new inhibitor, named eimbinostat, holds significant promise as potential therapeutic agent treatment hematologic malignancies such or leukemia.

Язык: Английский

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The association of FAT1 mutations with therapeutic outcomes in AML, especially in receiving venetoclax combination

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Март 31, 2025

Objective The role of FAT1 mutations in acute myeloid leukemia (AML) remains unclear, particularly regarding their impact on the chemosensitivity AML patients. To elucidate effect therapeutic outcomes and prognosis patients, we conducted this study. Methods analyze mutations, obtained data from LAML-KR cohort International Cancer Genome Consortium (ICGC), consisting 205 Additionally, retrospectively collected 108 primary patients who received initial induction chemotherapy with a venetoclax combination regimen between January 2019 December 2023 at Qingdao Medical College Affiliated Hospital Shengli Oilfield Central (referred to as Venetoclax-AML cohort). We analyzed characteristics, clinical features, molecular genetic features assessed both cohorts. Results In public (n = 205), mutation rate gene was approximately 15% (31/205), nonsynonymous about 6%. Patients (including synonymous mutations) exhibited higher tumor burden (TMB) compared wild-type (p &lt; 0.001). Further analysis 83 complete showed that rates P53, DNMT3A, FLT3, NPM1 genes were mutant group than 0.05). our retrospective 108), 13% (14/108), which cohort. Moreover, only P53 0.01), while no significant difference &gt; cohorts, better However, cohort, there improvement overall survival (OS) for (median time: 34.6 months vs. 41.7 months, p 0.6757), whereas trend toward improved progression-free (PFS) 0.103).Interestingly, further 17) revealed had PFS 0.1381). Conclusion have efficacy venetoclax-based regimens is PFS. This may be related mutation-positive

Язык: Английский

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Innovative evaluation of selinexor and JQ1 synergy in leukemia therapy via C-MYC inhibition

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Май 8, 2025

Acute myeloid leukemia (AML) remains a therapeutic challenge due to drug resistance and relapse. Selinexor, an XPO1 inhibitor, shows limited efficacy as monotherapy, necessitating combination strategies. JQ1, BET inhibitor targeting MYC, may synergize with Selinexor enhance antileukemic effects. AML cell lines, primary patient samples, xenograft models (MLL-AF9, CDX, PDX) were treated JQ1 alone or combined. Synergy was assessed via viability assays (Compusyn/SynergyFinder), apoptosis (flow cytometry/Western blot), C-MYC suppression (qPCR/CRISPR). In vivo evaluated by tumor burden cytometry) survival. The demonstrated strong synergy (CI < 1, HSA > 10) across models, 80% inhibition in lines samples. Mechanistically, it suppressed (protein/mRNA), induced (cleaved PARP), arrested cycle. vivo, the reduced leukemic bone marrow, spleen, liver, extending survival xenografts. PDX confirmed cells. synergistically target dual inhibition, offering promising strategy overcome resistance. Further clinical evaluation is warranted.

Язык: Английский

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