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    GENE:

    NPM1 (Nucleophosmin 1)

    i
    Other names: Nucleophosmin (Nucleolar Phosphoprotein B23, Numatrin), Testicular Tissue Protein Li 128, Nucleolar Protein NO38, Numatrin, NPM1, Nucleophosmin 1, Nucleophosmin/Nucleoplasmin Family, Member 1, Nucleolar Phosphoprotein B23
    1d
    A Study of Revumenib and Mezigdomide in People With Leukemia (clinicaltrials.gov)
    P1/2, N=52, Recruiting, Memorial Sloan Kettering Cancer Center
    New P1/2 trial
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    NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • NUP98 (Nucleoporin 98 And 96 Precursor 2)
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    MSK-IMPACT
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    Revuforj (revumenib) • mezigdomide (CC-92480)
    1d
    PRDM16 expression is an independent prognostic factor in AML with the double-mutant NPM1/FLT3-ITD genotype. (PubMed, Ann Hematol)
    These results suggest an association of PRDM16 overexpression with the NPM1/FLT3-ITD/DNMT3A triple-mutant AML genotype, typically linked to high leukemia stem cell frequencies and poor prognosis. Importantly, within this adverse AML subtype low PRDM16 expression is an independent prognostic marker for favorable outcome, supporting an anti-leukemic mechanism in AMLs with repressed PRDM16 transcription.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • PRDM16 (PR/SET Domain 16)
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    FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • TET2 mutation • IDH1 R132
    6d
    FBXO11 suppression rewires an NPM1-centered interactome influencing the progression of myelodysplastic syndrome. (PubMed, J Clin Invest)
    Finally, we discovered rare mutations in FBXO11, which mapped to a previously unstudied functional intrinsically disordered region (IDR) in the N-terminus responsible for binding NPM1. These data support a model in which FBXO11 rewires RNA binding and ribosomal subnetworks through ubiquitylation of NPM1, ultimately restricting MDS progression.
    Journal
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    NPM1 (Nucleophosmin 1) • CD34 (CD34 molecule) • FBXO11 (F-Box Protein 11) • CCNF (Cyclin F) • TLR2 (Toll Like Receptor 2)
    8d
    Unravelling co-mutational patterns with prognostic implications in NPM1 mutated adult acute myeloid leukemia - a HARMONY study. (PubMed, Leukemia)
    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) showed the highest benefit in the NPM1-mut adverse-risk subgroup. The HARMONY classification provides the basis for a refined genetic risk stratification for adult NPM1-mut AML with potential clinical impact on allo-HSCT decision-making.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2)
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    FLT3-ITD mutation • FLT3 mutation • NPM1 mutation
    9d
    Abnormal PLK2 expression is associated with specific subtypes and may help risk stratification in acute myeloid leukemia. (PubMed, Discov Oncol)
    Bioinformatics analysis demonstrated high PLK2 expression was positively associated with oncogenes such as FAM163A, CTNND2, DAAM2, PITX1, POU1F1, mir-196a and negatively associated with tumor suppressors such as EMX2, PADI3, CDO1, SHOX2 and mir-508. In conclusion, the research elaborates on the expression profile and the clinical significance of PLK2 gene in AML, suggesting PLK2 expression may help risk stratification and hypothesis-generating for HSCT decision support.
    Journal
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    TP53 (Tumor protein P53) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • MIR508 (MicroRNA 508) • PLK2 (Polo Like Kinase 2) • SHOX2 (SHOX Homeobox 2)
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    TP53 mutation • NPM1 mutation
    10d
    NPM1 and IDH1/2 Mutations Show Limited Prognostic Impact in Relapsed/Refractory AML: Evidence From the AVALON Cohort. (PubMed, Hematol Oncol)
    In the AVALON cohort of relapsed/refractory AML treated with venetoclax plus hypomethylating agents, NPM1 and IDH1/2 mutations showed no significant impact on response or survival. These findings indicate that prognostic models for relapsed AML should consider treatment context rather than baseline mutation status.
    Journal
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    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1)
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    NPM1 mutation
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    Venclexta (venetoclax)
    10d
    NCI-2017-02296: Testing Olaparib in Patients With Advanced or Metastatic (Cancer That Has Spread) Bladder Cancer and Other Genitourinary Tumors With DNA-Repair Genetic Changes (clinicaltrials.gov)
    P2, N=60, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026
    Trial completion date • Trial primary completion date • Tumor mutational burden
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    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ABL1 (ABL proto-oncogene 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • NPM1 (Nucleophosmin 1) • POLE (DNA Polymerase Epsilon) • CCND1 (Cyclin D1) • BAP1 (BRCA1 Associated Protein 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • BRD4 (Bromodomain Containing 4) • DOT1L (DOT1 Like Histone Lysine Methyltransferase) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • FANCC (FA Complementation Group C)
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    PALB2 mutation • BRIP1 mutation
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    FoundationOne® CDx • FoundationOne® Liquid CDx
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    Lynparza (olaparib)
    10d
    NPM1 in Aging-Related Multi-System Diseases: Molecular Mechanisms and Therapeutic Implications. (PubMed, Aging Dis)
    Although growing evidence highlights the potential of NPM1 inhibitors to modulate signaling cascades and improve clinical outcomes, context-selective inhibition of NPM1 may unexpectedly worsen disease progression in certain settings, underscoring its functionally dual nature depending on the context of the disease. This review delineates NPM1 signaling as a central orchestrator in aging-related pathogenesis and supports its potential as a therapeutic target to enhance treatment efficacy.
    Review • Journal
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    NPM1 (Nucleophosmin 1)
    11d
    Cup-Like Blasts in B-Lymphoblastic Leukemia with KMT2A Rearrangement: A Rare Morphological Presentation. (PubMed, Indian J Hematol Blood Transfus)
    This case adds to the limited literature reporting cup-like nuclear morphology in B-ALL, which is typically associated with varied cytogenetic abnormalities, including BCR::ABL1 fusion and hyperdiploidy [3, 4]. The findings emphasize the critical role of FCI and molecular studies in distinguishing AML from B-ALL or mixed phenotype acute leukemias.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A) • IKZF1 (IKAROS Family Zinc Finger 1) • FUT4 (Fucosyltransferase 4)
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    FLT3-ITD mutation • NPM1 mutation • KMT2A rearrangement • ABL1 fusion
    13d
    AML Disparities Across Racial Ancestry Groups: A Spotlight on the NPM1 Mutations. (PubMed, Int J Mol Sci)
    Thus, treatment algorithms and prognostic systems based on outcomes from a single racial ancestry group are inadequate. Beyond the more traditional socioeconomic determinants of health, addressing disparities in AML to achieve equity in care requires exploring biological factors linked to ancestry that shape treatment response.
    Review • Journal
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    NPM1 (Nucleophosmin 1)
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    NPM1 mutation
    13d
    Characterizing KMT2A Rearrangement in Acute Myeloid Leukemia: A Comprehensive Genomic Study. (PubMed, Cancers (Basel))
    No amplifications or deletions were seen. This genomic landscape study highlights significant genomic differences between KMT2Ar and KMT2Awt AML patients, which may enrich our understanding of the molecular profile and clusters of mutations in AML.
    Journal
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2)
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    KRAS G12C • KMT2A rearrangement • KRAS G12 • MLL mutation
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    FoundationOne® Heme CDx