{"doi":"10.1182/blood.2020008211","title":"How I diagnose and treat<i>NPM1</i>-mutated AML","abstract":"<jats:title>Abstract</jats:title><jats:p>Mutations of the nucleophosmin (NPM1) gene, encoding for a nucleolar multifunctional protein, occur in approximately one-third of adult acute myeloid leukemia (AML). NPM1-mutated AML exhibits unique molecular, pathological, and clinical features, which led to its recognition as distinct entity in the 2017 World Health Organization (WHO) classification of myeloid neoplasms. Although WHO criteria for the diagnosis of NPM1-mutated AML are well established, its distinction from other AML entities may be difficult. Moreover, the percentage of blasts required to diagnose NPM1-mutated AML remains controversial. According to the European LeukemiaNet (ELN), determining the mutational status of NPM1 (together with FLT3) is mandatory for accurate relapse-risk assessment. NPM1 mutations are ideal targets for measurable residual disease (MRD) monitoring, since they are AML specific, frequent, very stable at relapse, and do not drive clonal hematopoiesis of undetermined significance. MRD monitoring by quantitative polymerase chain reaction of NPM1-mutant transcripts, possibly combined with ELN genetic-based risk stratification, can guide therapeutic decisions after remission. Furthermore, immunohistochemistry can be very useful in selected situations, such as diagnosis of NPM1-mutated myeloid sarcoma. Herein, we present 4 illustrative cases of NPM1-mutated AML that address important issues surrounding the biology, diagnosis, and therapy of this common form of leukemia.</jats:p>","journal":"Blood","year":2021,"id":597650,"datarank":0.6456097639806255,"base_score":4.304065093204169,"endowment":4.304065093204169,"self_citation_contribution":0.6456097639806255,"citation_network_contribution":0.0,"self_endowment_contribution":0.6456097639806255,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":73,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":18362,"name":"Lorenzo Brunetti","orcid":"0000-0003-2624-8576","position":1,"is_corresponding":false},{"id":376677,"name":"Maria Paola Martelli","orcid":"0000-0001-9139-1729","position":2,"is_corresponding":false},{"id":87416,"name":"Brunangelo Falini","orcid":"0000-0002-7198-5965","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"How I diagnose and treat<i>NPM1</i>-mutated AML","abstract":"<jats:title>Abstract</jats:title><jats:p>Mutations of the nucleophosmin (NPM1) gene, encoding for a nucleolar multifunctional protein, occur in approximately one-third of adult acute myeloid leukemia (AML). NPM1-mutated AML exhibits unique molecular, pathological, and clinical features, which led to its recognition as distinct entity in the 2017 World Health Organization (WHO) classification of myeloid neoplasms. Although WHO criteria for the diagnosis of NPM1-mutated AML are well established, its distinction from other AML entities may be difficult. Moreover, the percentage of blasts required to diagnose NPM1-mutated AML remains controversial. According to the European LeukemiaNet (ELN), determining the mutational status of NPM1 (together with FLT3) is mandatory for accurate relapse-risk assessment. NPM1 mutations are ideal targets for measurable residual disease (MRD) monitoring, since they are AML specific, frequent, very stable at relapse, and do not drive clonal hematopoiesis of undetermined significance. MRD monitoring by quantitative polymerase chain reaction of NPM1-mutant transcripts, possibly combined with ELN genetic-based risk stratification, can guide therapeutic decisions after remission. Furthermore, immunohistochemistry can be very useful in selected situations, such as diagnosis of NPM1-mutated myeloid sarcoma. Herein, we present 4 illustrative cases of NPM1-mutated AML that address important issues surrounding the biology, diagnosis, and therapy of this common form of leukemia.</jats:p>","is_dataset_classified":null,"base_score":4.304065093204169,"endowment":4.304065093204169,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33171486","pmcid":null,"openalex_id":"https://openalex.org/W3102223894","authors":[],"funders":[{"funder_name":"European Commission","grant_id":"740230","title":"Improving therapy of NPM1-mutated AML"},{"funder_name":"European Commission","grant_id":"725725","title":"Dissecting to hit the therapeutic targets in nucleophosmin (NPM1)-mutated acute myeloid leukemia"}],"total_grants":2,"fwci":5.489,"citation_percentile":0.97069442,"influential_citations":0,"citation_trend":[{"year":2020,"count":1},{"year":2021,"count":14},{"year":2022,"count":16},{"year":2023,"count":17},{"year":2024,"count":10},{"year":2025,"count":9},{"year":2026,"count":6}],"oa_status":"bronze","license":"other-oa","oa_locations":[{"url":"https://ashpublications.org/blood/article-pdf/137/5/589/1798866/bloodbld2020008211.pdf","host_type":"journal"},{"url":"https://ashpublications.org/blood/article-pdf/137/5/589/1798866/bloodbld2020008211.pdf","host_type":"publisher"},{"url":"http://ashpublications.org/blood/article-pdf/137/5/589/1798866/bloodbld2020008211.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1182/blood.2020008211","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33171486","host_type":"repository"},{"url":"https://ashpublications.org/blood/article/137/5/589/474131/How-I-diagnose-and-treat-NPM1-mutated-AML","host_type":"repository"},{"url":"https://iris.univpm.it/bitstream/11566/293286/2/Falini_How-diagnose-treat-NPM1-mutated_2021.pdf","host_type":"repository"},{"url":"https://dx.doi.org/10.1182/blood.2020008211","host_type":""},{"url":"http://dx.doi.org/10.1182/blood.2020008211","host_type":""}],"fields_of_study":["Acute Myeloid Leukemia Research","Myeloproliferative Neoplasms: Diagnosis and Treatment","Sarcoma Diagnosis and Treatment","0301 basic medicine","0303 health sciences","03 medical and health sciences","Age Factors","Aged","Algorithms","Allografts","Antineoplastic Combined Chemotherapy Protocols","Bone Marrow","Bridged Bicyclo Compounds, Heterocyclic","Cell Lineage","Clinical Trials as Topic","Clonal Evolution","Combined Modality Therapy","Diagnosis, Differential","Disease Management","Female","Gemtuzumab","Hematopoietic Stem Cell Transplantation","Humans","Leukemia, Myeloid, Acute","Male","Middle Aged","Molecular Targeted Therapy","Myelodysplastic Syndromes","Neoplastic Stem Cells","Nuclear Proteins","Nucleophosmin","Oncogene Proteins, Fusion","Patient Selection","Practice Patterns, Physicians'","Remission Induction","Risk Assessment","Salvage Therapy","Sulfonamides","fms-Like Tyrosine Kinase 3"],"mesh_terms":["Gemtuzumab","Nucleophosmin","Age Factors","Aged","Algorithms","Antineoplastic Combined Chemotherapy Protocols","Bone Marrow","Clinical Trials as Topic","Combined Modality Therapy","Diagnosis, Differential","Female","Humans","Male","Middle Aged","Myelodysplastic Syndromes","Nuclear Proteins","Practice Patterns, Physicians'","Remission Induction","Sulfonamides","Neoplastic Stem Cells","Leukemia, Myeloid, Acute","Oncogene Proteins, Fusion","Salvage Therapy","Hematopoietic Stem Cell Transplantation","Risk Assessment","Patient Selection","Cell Lineage","Bridged Bicyclo Compounds, Heterocyclic","Disease Management","fms-Like Tyrosine Kinase 3","Molecular Targeted Therapy","Clonal Evolution","Allografts"],"keywords":["NPM1","Nucleophosmin","Myeloid leukemia","Medicine","Minimal residual disease","CEBPA","Leukemia","Oncology","Cancer research","Internal medicine","Mutation","Gene","Biology","Genetics","Karyotype","Male","Clinical Trials as Topic","Age Factors","Hematopoietic Stem Cell Transplantation","Disease Management","Middle Aged","Allografts","Bridged Bicyclo Compounds, Heterocyclic","Combined Modality Therapy","Gemtuzumab","Clonal Evolution","Diagnosis, Differential","Leukemia, Myeloid, Acute","Bone Marrow","Antineoplastic Combined Chemotherapy Protocols","Humans","Cell Lineage","Female","Algorithms","Aged"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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