Influence of Nucleophosmin ( NPM1 ) Genotypes on Outcome of Patients With AML: An AIEOP-BFM and COG-SWOG Intergroup Collaboration DOI
Claudia Tregnago, Maddalena Benetton, Rhonda E. Ries

et al.

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 43(8), P. 972 - 984

Published: Dec. 2, 2024

Several genomic subsets of NPM1 mutations with varying sequences (type A, B, D, etc) have been identified. Despite molecular heterogeneity, cumulatively portend a more favorable outcome, but biology and prognostic implications different not extensively studied. In this multicentric study, we investigated the impact genotypes on patient's outcomes interrogated underlying subtypes. Of than 4,000 patients enrolled in multiple pediatric cooperative (AIEOP, BFM, ELAM02, NOPHO, DCOG, COG trials), or adult (SWOG) trials, 348 75 AML known genotype available outcome were selected for study. Diverse variants correlated probabilities overall survival (OS) event-free survival. Nuclear localization translational efficiency was Evaluation clinical basis showed that type other rare had similarly outcomes, whereas those D significantly worse (OS 63% v 86% non-D, P = .005). Multivariate analysis confirmed as an independent factor associated inferior OS (hazard ratio, 3; vitro, demonstrated versus A synonymous variants, codon optimality plays major roles determining gene expression levels, translation efficiency, which resulted expressed NPM1-D mRNA protein, mediating peculiar mitochondrial expression. The evaluation specific identified being suggesting reclassification cases to higher-risk groups.

Language: Английский

Monocytic Differentiation in Acute Myeloid Leukemia Cells: Diagnostic Criteria, Biological Heterogeneity, Mitochondrial Metabolism, Resistance to and Induction by Targeted Therapies DOI Open Access
Øystein Bruserud, Frode Selheim, Maria Hernandez-Valladares

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6356 - 6356

Published: June 8, 2024

We review the importance of monocytic differentiation and induction in non-APL (acute promyelocytic leukemia) variants acute myeloid leukemia (AML), a malignancy characterized by proliferation immature cells. Even though cellular block is fundamental characteristic, AML cells can show limited signs differentiation. According to French-American-British (FAB-M4/M5 subset) World Health Organization (WHO) 2016 classifications, morphological expression specific molecular markers involved communication adhesion. Furthermore, FAB-M4/M5 patients are heterogeneous with regards cytogenetic genetic abnormalities, does not have any major prognostic impact for these when receiving conventional intensive cytotoxic therapy. In contrast, decreased susceptibility Bcl-2 inhibitor venetoclax, this seems be due common characteristics involving mitochondrial regulation metabolism survival, including dependency on compared other patients. Thus, inhibition only depend general resistance/susceptibility mechanisms known from therapy but also target itself or context target. cell status associated targeted therapies (e.g., CDK2/4/6 bromodomain inhibition), part antileukemic effect several anti-AML therapies. Differentiation-associated may thus become important future implementation human AML.

Language: Английский

Citations

5
Large-scale screens identify a 19-Gene MitoScore for improved risk assessment in acute myeloid leukemia DOI

Liting Niu,

Hanfei Guo, Yijing Zhao

et al.

Mitochondrion, Journal Year: 2025, Volume and Issue: 82, P. 102011 - 102011

Published: Feb. 20, 2025

Language: Английский

Citations

0
Drug Sensitivity patterns across FAB subtypes and molecular mutations in AML: A comprehensive analysis for precision medicine DOI Creative Commons

Mohan Krishna Shrestha,

Bishwas Mandal,

Vishal Mandal

et al.

Clinical and Translational Discovery, Journal Year: 2025, Volume and Issue: 5(2)

Published: March 22, 2025

Abstract Background Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by distinct French–American–British (FAB) classifications and molecular mutations. Understanding how these biological markers relate to drug responses crucial for refining therapeutic approaches. Methods We examined sensitivity patterns in 186 AML patients using selective Drug Sensitivity Scores (sDSS), analysing data from 515 commercially available chemotherapeutic targeted oncology agents. was analysed across various FAB subtypes (M0, M1, M2, M4, M4 eos, M4/M5, M5) important mutations (NPM1, FLT3, FLT3‐ITD, FLT3‐TKD KIT). Results Navitoclax showed greater effectiveness M0, M2 subtypes. NPM1 were linked increased multiple FLT3‐ITD associated with significant responsiveness PI3K/mTOR inhibitors. Analysis of combinations revealed complexities agents, often leading reduced but providing insights into successful pairings. Conclusions The findings underscore the necessity personalised strategies AML, advocating treatment protocols that integrate individual mutation profiles enhance patient care improve clinical outcomes.

Language: Английский

Citations

0
Mechanisms of chemotherapy failure in refractory/relapsed acute myeloid leukemia: the role of cytarabine resistance and mitochondrial metabolism DOI Creative Commons

Soo Yeon Chae,

Se‐Young Jang,

Ji Hoon Kim

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 23, 2025

Language: Английский

Citations

0
Mitohormesis : la clé de voûte de la résistance thérapeutique des cellules cancéreuses DOI Creative Commons
Emeline Boët, Estelle Saland, Sarah Skuli

et al.

Comptes Rendus Biologies, Journal Year: 2024, Volume and Issue: 347(G1), P. 59 - 75

Published: Aug. 22, 2024

A large body of literature highlights the importance energy metabolism in response haematological malignancies to therapy. In this review, we are particularly interested acute myeloid leukaemia, where mitochondrial plays a key role and resistance treatment. We describe new concept mitohormesis therapy-induced stress initiation relapse disease.

Language: Английский

Citations

0
Influence of Nucleophosmin ( NPM1 ) Genotypes on Outcome of Patients With AML: An AIEOP-BFM and COG-SWOG Intergroup Collaboration DOI
Claudia Tregnago, Maddalena Benetton, Rhonda E. Ries

et al.

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 43(8), P. 972 - 984

Published: Dec. 2, 2024

Several genomic subsets of NPM1 mutations with varying sequences (type A, B, D, etc) have been identified. Despite molecular heterogeneity, cumulatively portend a more favorable outcome, but biology and prognostic implications different not extensively studied. In this multicentric study, we investigated the impact genotypes on patient's outcomes interrogated underlying subtypes. Of than 4,000 patients enrolled in multiple pediatric cooperative (AIEOP, BFM, ELAM02, NOPHO, DCOG, COG trials), or adult (SWOG) trials, 348 75 AML known genotype available outcome were selected for study. Diverse variants correlated probabilities overall survival (OS) event-free survival. Nuclear localization translational efficiency was Evaluation clinical basis showed that type other rare had similarly outcomes, whereas those D significantly worse (OS 63% v 86% non-D, P = .005). Multivariate analysis confirmed as an independent factor associated inferior OS (hazard ratio, 3; vitro, demonstrated versus A synonymous variants, codon optimality plays major roles determining gene expression levels, translation efficiency, which resulted expressed NPM1-D mRNA protein, mediating peculiar mitochondrial expression. The evaluation specific identified being suggesting reclassification cases to higher-risk groups.

Language: Английский

Citations

0