Genetic, Phenotypic, and Clinical Heterogeneity of NPM1-Mutant Acute Myeloid Leukemias

Testa, Ugo; Pelosi, Elvira; Castelli, Germana

doi:10.3390/biomedicines11071805

Cited by 2 publications

(1 citation statement)

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“…Due to its unique clinical and molecular features, the World Health Organization (WHO) Classification of Haemato-lymphoid Tumours [4] identifies the NPM1-mutated (mut) AML as a distinct entity irrespective of blast counts, known as "AML with mutated NPM1". NPM1mut is frequently associated with a normal karyotype and can manifest independently or in conjunction with additional genetic variations affecting genes such as FLT3, DNMT3a, IDH1, IDH2, and TET2 [5]. According to the WHO Classification, NPM1mut AML patients without any other genetic abnormalities are associated with a more favorable prognosis compared to other AML subtypes [4].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Molecular Profiling of NPM1-Mutated Acute Myeloid Leukemia Using RNAseq Approach

Petiti,

Pignochino,

Schiavon

et al. 2024

IJMS

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Acute myeloid leukemia (AML) is a complex hematologic malignancy with high morbidity and mortality. Nucleophosmin 1 (NPM1) mutations occur in approximately 30% of AML cases, and NPM1-mutated AML is classified as a distinct entity. NPM1-mutated AML patients without additional genetic abnormalities have a favorable prognosis. Despite this, 30–50% of them experience relapse. This study aimed to investigate the potential of total RNAseq in improving the characterization of NPM1-mutated AML patients. We explored genetic variations independently of myeloid stratification, revealing a complex molecular scenario. We showed that total RNAseq enables the uncovering of different genetic alterations and clonal subtypes, allowing for a comprehensive evaluation of the real expression of exome transcripts in leukemic clones and the identification of aberrant fusion transcripts. This characterization may enhance understanding and guide improved treatment strategies for NPM1mut AML patients, contributing to better outcomes. Our findings underscore the complexity of NPM1-mutated AML, supporting the incorporation of advanced technologies for precise risk stratification and personalized therapeutic strategies. The study provides a foundation for future investigations into the clinical implications of identified genetic variations and highlights the importance of evolving diagnostic approaches in leukemia management.

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Section: Introductionmentioning

confidence: 99%

Comprehensive Molecular Profiling of NPM1-Mutated Acute Myeloid Leukemia Using RNAseq Approach

Petiti,

Pignochino,

Schiavon

et al. 2024

IJMS

View full text Add to dashboard Cite

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Influence of genetic co‐mutation on chemotherapeutic outcome in NPM1‐mutated and FLT3‐ITD wild‐type AML patients

Wu,

Zhang,

Yuan

et al. 2024

Cancer Medicine

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BackgroundNucleophosmin 1 (NPM1) gene‐mutated acute myeloid leukemia (NPM1mut AML) is classified as a subtype with a favorable prognosis. However, some patients fail to achieve a complete remission or relapse after intensified chemotherapy. Genetic abnormalities in concomitant mutations contribute to heterogeneous prognosis of NPM1mut AML patients.MethodsIn this study, 91 NPM1‐mutated and FLT3‐ITD wild‐type (NPM1mut/FLT3‐ITDwt) AML patients with intermediate‐risk karyotype were enrolled to analyze the impact of common genetic co‐mutations on chemotherapeutic outcome.ResultsOur data revealed that TET1/2 (52/91, 57.1%) was the most prevalent co‐mutation in NPM1mut AML patients, followed by IDH1/2 (36/91, 39.6%), DNMT3A (35/91, 38.5%), myelodysplastic syndrome related genes (MDS‐related genes) (ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1 and ZRSR2 genes) (35/91, 38.5%), FLT3‐TKD (27/91, 29.7%) and GATA2 (13/91, 14.3%) mutations. Patients with TET1/2mut exhibited significantly worse relapse‐free survival (RFS) (median, 28.7 vs. not reached (NR) months; p = 0.0382) compared to patients with TET1/2wt, while no significant difference was observed in overall survival (OS) (median, NR vs. NR; p = 0.3035). GATA2mut subtype was associated with inferior OS (median, 28 vs. NR months; p < 0.0010) and RFS (median, 24 vs. NR months; p = 0.0224) compared to GATA2wt. By multivariate analysis, GATA2mut and MDS‐related genesmut were independently associated with worse survival.ConclusionMutations in TET1/2, GATA2 and MDS‐related genes were found to significantly influence the chemotherapeutic outcome of patients with NPM1mut AML. The findings of our study have significant clinical implications for identifying patients who have an adverse response to frontline chemotherapy and provide a novel reference for further prognostic stratification of NPM1mut/FLT3‐ITDwt AML patients.

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Genetic, Phenotypic, and Clinical Heterogeneity of NPM1-Mutant Acute Myeloid Leukemias

Cited by 2 publications

References 123 publications

Comprehensive Molecular Profiling of NPM1-Mutated Acute Myeloid Leukemia Using RNAseq Approach

Comprehensive Molecular Profiling of NPM1-Mutated Acute Myeloid Leukemia Using RNAseq Approach

Influence of genetic co‐mutation on chemotherapeutic outcome in NPM1‐mutated and FLT3‐ITD wild‐type AML patients

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