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    BIOMARKER:

    NPM1 mutation + DNMT3A mutation

    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, DNMT3A, DNA Methyltransferase 3 Alpha, DNA (Cytosine-5-)-Methyltransferase 3 Alpha, DNA (Cytosine-5)-Methyltransferase 3A, DNA MTase HsaIIIA, DNA Cytosine Methyltransferase 3A2, DNA Methyltransferase HsaIIIA, DNMT3A2, Dnmt3a
    Entrez ID:
    4869; 1788
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    4years
    [VIRTUAL] Genetic Features of AML with MLL-Rearrangement and NPM1 Mutation: An Interim-Analysis of HM-Screen-Japan 01 (ASH 2020)
    "MLL-rearrangements and NPM1-mutations were found in approximately a quarter of the 91 AML patient (mostly relapsed or refractory) bone marrow samples analyzed. These alterations appeared to be mutually exclusive. FLT3 alterations were seen in a third of the MLL-AML cases and half of the NPM1-AML cases, seemingly more frequent than that previously reported."
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • ETV6 (ETS Variant Transcription Factor 6) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • NTRK (Neurotrophic receptor tyrosine kinase) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
    |
    TP53 mutation • NRAS mutation • FLT3-ITD mutation • IDH1 mutation • IDH2 mutation • FLT3 mutation • NPM1 mutation • DNMT3A mutation • ETV6-NTRK3 fusion • TET2 mutation • PTPN11 mutation • MLL rearrangement • FLT3 mutation + DNMT3A mutation • NPM1 mutation + DNMT3A mutation • MLL fusion • NPM1 mutation + NRAS mutation
    |
    FoundationOne® Heme CDx
    4years
    [VIRTUAL] Emergence ofNPM1Wild-Type Myeloid Neoplasms after Chemotherapy for Acute Leukemia withNPM1Mutation: Proposed Mechanisms of Clonal Evolution (ASH 2020)
    Conclusions A proportion of pts withNPM1mut-AML will develop an NPM1 wild-type myeloid neoplasm after intensive chemotherapy-induced CR, emerging from preleukemic clonal hematopoiesis. Given this possible evolution, which can not be predicted byNPM1mutmeasurable residual disease monitoring, an active surveillance of these pts is recommended, including genetic re-testing at time of disease relapse or progression.
    TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • SETBP1 (SET Binding Protein 1) • AGER (Advanced Glycosylation End-Product Specific Receptor)
    |
    NPM1 mutation • DNMT3A mutation • ASXL1 mutation • NPM1 mutation + DNMT3A mutation
    |
    Oncomine Myeloid Assay GX
    4years
    Co-occurrence of DNMT3A, NPM1, FLT3 mutations identifies a subset of acute myeloid leukemia with adverse prognosis. (PubMed, Blood)
    No abstract available
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)
    |
    FLT3 mutation • NPM1 mutation • DNMT3A mutation • FLT3 mutation + DNMT3A mutation • NPM1 mutation + DNMT3A mutation
    4years
    Characteristics and prognostic significance of genetic mutations in acute myeloid leukemia based on a targeted next-generation sequencing technique. (PubMed, Cancer Med)
    According to multivariate analysis, TET2 mutation was recognized as an independent prognostic factors for RFS. In summary, our study provided a detailed pattern of gene mutations and their prognostic relevance in Chinese AML patients based on targeted next-generation sequencing screening.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    NRAS mutation • FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • ASXL1 mutation • TET2 mutation • CEBPA mutation • FLT3 mutation + NPM1 mutation • FLT3 mutation + DNMT3A mutation • NPM1 mutation + DNMT3A mutation • NPM1 mutation + NRAS mutation
    4years
    Lomustine is beneficial to older AML with ELN2017 adverse risk profile and intermediate karyotype: a FILO study. (PubMed, Leukemia)
    A molecular analysis of 52 genes performed in 330 patients included in this trial, 163 patients being treated with lomustine in combination with idarubicin and cytarabine and 167 without lomustine, identified 1088 mutations with an average of 3.3 mutations per patient. The benefit of lomustine in nonadverse chromosomal aberrations was restricted to patients with RUNX1, ASXL1, TP53, and FLT3-ITD/NPM1 mutations in contrast to the intermediate and favorable ELN2017 patients. This post-hoc analysis identified a subgroup of fit elderly AML patients with intermediate cytogenetics and molecular markers who may benefit from lomustine addition to intensive chemotherapy.
    Journal
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1)
    |
    FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • ASXL1 mutation • FLT3 mutation + NPM1 mutation • FLT3 mutation + DNMT3A mutation • NPM1 mutation + DNMT3A mutation
    |
    cytarabine • idarubicin hydrochloride • lomustine
    over4years
    [VIRTUAL] The genesis of AML influences the prognostic relevance of the stem cell markers CD34 + / CD38- cell load and GPR56 expression after allogeneic stem cell transplantation (DGHO 2020)
    We analyzed 379 AML pts who received a HSCT in complete remission (CR, 82%) or CR with incomplete peripheral recovery (CRi, 18%) after non-myeloablative (3x30 mg/m2 Fludarabine & 2 Gy total body irradiation) conditioning...A high CD34+/CD38- burden & high GPR56 expression at diagnosis only impacted outcome in de novo AML pts. Different LSC populations may be relevant for disease biology in s/tAML.
    IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • CD38 (CD38 Molecule) • CD34 (CD34 molecule)
    |
    FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • FLT3 mutation + DNMT3A mutation • NPM1 mutation + DNMT3A mutation
    |
    fludarabine IV
    over4years
    [VIRTUAL] The genesis of AML influences the prognostic relevance of the stem cell markers CD34 + / CD38- cell load and GPR56 expression after allogeneic stem cell transplantation (DGHO 2020)
    We analyzed 379 AML pts who received a HSCT in complete remission (CR, 82%) or CR with incomplete peripheral recovery (CRi, 18%) after non-myeloablative (3x30 mg/m2 Fludarabine & 2 Gy total body irradiation) conditioning...A high CD34+/CD38- burden & high GPR56 expression at diagnosis only impacted outcome in de novo AML pts. Different LSC populations may be relevant for disease biology in s/tAML.
    IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • CD38 (CD38 Molecule) • CD34 (CD34 molecule)
    |
    FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • FLT3 mutation + DNMT3A mutation • NPM1 mutation + DNMT3A mutation
    |
    fludarabine IV
    over4years
    [VIRTUAL] The genesis of AML influences the prognostic relevance of the stem cell markers CD34 + / CD38- cell load and GPR56 expression after allogeneic stem cell transplantation (DGHO 2020)
    We analyzed 379 AML pts who received a HSCT in complete remission (CR, 82%) or CR with incomplete peripheral recovery (CRi, 18%) after non-myeloablative (3x30 mg/m2 Fludarabine & 2 Gy total body irradiation) conditioning...A high CD34+/CD38- burden & high GPR56 expression at diagnosis only impacted outcome in de novo AML pts. Different LSC populations may be relevant for disease biology in s/tAML.
    IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • CD38 (CD38 Molecule) • CD34 (CD34 molecule)
    |
    FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • FLT3 mutation + DNMT3A mutation • NPM1 mutation + DNMT3A mutation
    |
    fludarabine IV
    over4years
    Clinical Significance of Common Gene Mutations in 53 Patients with Acute Myeloid Leukemia Harboring 11q23/MLL Rearrangements (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
    A relatively high mutation frequency is observed in AML patients with 11q23/MLL rearrangements and most cases shows single mutation. The RAS signaling pathway alterations are most common. Gene mutation does not affect the OS of these patients, who show poor prognosis. A significantly higher Hb at initial diagnosis in FLT3 mutated patients is significantly higher than that in FLT3 wild-type cases. Patients who underwent HSCT show a better prognosis than those only received chemotherapy.
    Clinical • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    NRAS mutation • FLT3-ITD mutation • FLT3 mutation • NPM1 mutation • KIT mutation • DNMT3A mutation • ASXL1 mutation • TET2 mutation • EZH2 mutation • FLT3-TKD mutation • MLL rearrangement • CEBPA mutation • DNMT3A mutation + FLT3-ITD mutation • WT1 mutation • FLT3 mutation + DNMT3A mutation • FLT3-ITD mutation + MLL rearrangement • NPM1 mutation + DNMT3A mutation • NPM1 mutation + NRAS mutation
    over4years
    Impact of the variant allele frequency of ASXL1, DNMT3A, JAK2, TET2, TP53, and NPM1 on the outcomes of patients with newly diagnosed acute myeloid leukemia. (PubMed, Cancer)
    The VAF of ASXL1, DNMT3A, JAK2, TET2, TP53, and NPM1 mutations is associated with worse prognosis in patients with newly diagnosed AML.
    Clinical • Journal
    |
    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2)
    |
    TP53 mutation • NPM1 mutation • DNMT3A mutation • ASXL1 mutation • TET2 mutation • JAK2 mutation • FLT3 mutation + DNMT3A mutation • NPM1 mutation + DNMT3A mutation
    over4years
    High Throughput Molecular Characterization of Normal Karyotype Acute Myeloid Leukemia in the Context of the Prospective Trial 02/06 of the Northern Italy Leukemia Group (NILG). (PubMed, Cancers (Basel))
    FLT3-ITD positive patients who proceeded to alloHSCT had a survival probability similar to FLT3-ITD negative patients and the transplant outcome was no different when comparing high and low-AR-FLT3-ITD subgroups in terms of both OS and DFS. In conclusion, a comprehensive molecular profile for NK-AML allows for the identification of genetic lesions associated to different clinical outcomes and the selection of the most appropriate and effective treatment strategies, including stem cell transplantation and targeted therapies.
    Clinical • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1)
    |
    FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • IDH1 R132H • FLT3 mutation + DNMT3A mutation • NPM1 mutation + DNMT3A mutation
    over4years
    Clinical Effect of Combined Mutations in DNMT3A, FLT3-ITD, and NPM1 Among Egyptian Acute Myeloid Leukemia Patients. (PubMed, Clin Lymphoma Myeloma Leuk)
    DNMT3A, FLT3-ITD, and NPM1A are frequent mutations in Egyptian AML. FLT3-ITD mutations are frequent in older patients. DNMT3A and FLT3-ITD mutations were associated with an unfavorable prognosis, but the NPM1A mutation has tendency to indicate a good prognosis.
    Clinical • Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)
    |
    FLT3-ITD mutation • NPM1 mutation • DNMT3A mutation • DNMT3A mutation + FLT3-ITD mutation • FLT3 mutation + DNMT3A mutation • NPM1 mutation + DNMT3A mutation