<i>NPM1</i> exon 5 mutations in acute myeloid leukemia: Implications in diagnosis and minimal residual monitoring

Wang, Peng; Segal, Jeremy P.; Drazer, Michael W.; Venkataraman, Girish; Arber, Daniel A.; Gurbuxani, Sandeep

doi:10.1002/jha2.445

Cited by 2 publications

(1 citation statement)

References 12 publications

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“…Immunohistochemistry may also help to identify multilineage dysplasia 34 and to diagnose cases with aplastic or necrotic BM resulting in dry tap. 42,43 Moreover, immunohistochemistry can predict NPM1 mutations occurring at exons other than 12 (e.g., exons 9, 11, and 5) 18,19,44,45 that may be missed by standard molecular assays. However, in NPM1 exon 5 mutations, cytoplasmic NPM1 is detected only by anti-N terminal NPM1 antibodies but not by the antibody specific for the mutant A.…”

Section: Diagnosis Of Npm1-mutated Amlmentioning

confidence: 99%

NPM1‐mutated acute myeloid leukemia: New pathogenetic and therapeutic insights and open questions

Falini

2023

American J Hematol

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The nucleophosmin (NPM1) gene encodes for a multifunctional chaperone protein that is localized in the nucleolus but continuously shuttles between the nucleus and cytoplasm. NPM1 mutations occur in about one‐third of AML, are AML‐specific, usually involve exon 12 and are frequently associated with FLT3‐ITD, DNMT3A, TET2, and IDH1/2 mutations. Because of its unique molecular and clinico‐pathological features, NPM1‐mutated AML is regarded as a distinct leukemia entity in both the International Consensus Classification (ICC) and the 5th edition of the World Health Organization (WHO) classification of myeloid neoplasms. All NPM1 mutations generate leukemic mutants that are aberrantly exported in the cytoplasm of the leukemic cells and are relevant to the pathogenesis of the disease. Here, we focus on recently identified functions of the NPM1 mutant at chromatin level and its relevance in driving HOX/MEIS gene expression. We also discuss yet controversial issues of the ICC/WHO classifications, including the biological and clinical significance of therapy‐related NPM1‐mutated AML and the relevance of blasts percentage in defining NPM1‐mutated AML. Finally, we address the impact of new targeted therapies in NPM1‐mutated AML with focus on CAR T cells directed against NPM1/HLA neoepitopes, as well as XPO1 and menin inhibitors.

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Section: Diagnosis Of Npm1-mutated Amlmentioning

confidence: 99%

NPM1‐mutated acute myeloid leukemia: New pathogenetic and therapeutic insights and open questions

Falini

2023

American J Hematol

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Criteria for Diagnosis and Molecular Monitoring of NPM1-Mutated AML

Falini,

Dillon

2023

Blood Cancer Discovery

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NPM1-mutated acute myeloid leukemia (AML) represents the largest molecular subgroup of adult AML. NPM1-mutated AML is recognizable by molecular techniques and immunohistochemistry which, when combined, can solve difficult diagnostic problems (including identification of myeloid sarcoma and NPM1 mutations outside exon 12). According to the 2022 European LeukemiaNet (ELN), determining the mutational status of NPM1 (and FLT3) is a mandatory step for the genetic-based risk stratification of AML. Monitoring of MRD by RT-qPCR, combined with ELN risk-stratification, can guide therapeutic decisions at post-remission stage. Here, we review the criteria for appropriate diagnosis and molecular monitoring of NPM1-mutated AML.

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NPM1 exon 5 mutations in acute myeloid leukemia: Implications in diagnosis and minimal residual monitoring

Cited by 2 publications

References 12 publications

NPM1‐mutated acute myeloid leukemia: New pathogenetic and therapeutic insights and open questions

NPM1‐mutated acute myeloid leukemia: New pathogenetic and therapeutic insights and open questions

Criteria for Diagnosis and Molecular Monitoring of NPM1-Mutated AML

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