DOI: 10.1182/blood-2005-08-3167. Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML)

Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML)

10.1182/blood-2005-08-3167

Crossref journal-article

American Society of Hematology

Blood (234)

Abstract

Mutations of the nucleophosmin (NPM1) gene have recently been described in patients with acute myeloid leukemia (AML). To clarify the prevalence as well as the clinical impact of this mutation, we investigated 1485 patients with AML for NPM1 exon 12 mutations using fragment analysis. A 4 bp insert was detected in 408 of 1485 patients (27.5%). Sequence analysis revealed known mutations (type A, B, and D) as well as 13 novel alterations in 229 analyzed cases. NPM1 mutations were most prevalent in patients with normal karyotype (NK) (324 of 709; 45.7%) compared with 58 of 686 with karyotype abnormalities (8.5%; P < .001) and were significantly associated with several clinical parameters (high bone marrow [BM] blasts, high white blood cell [WBC] and platelet counts, female sex). NPM1 alterations were associated with FLT3-ITD mutations, even if restricted to patients with NK (NPM1-mut/FLT3-ITD: 43.8%; versus NPM1-wt/FLT3-ITD: 19.9%; P < .001). The analysis of the clinical impact in 4 groups (NPM1 and FLT3-ITD single mutants, double mutants, and wild-type [wt] for both) revealed that patients having only an NPM1 mutation had a significantly better overall and disease-free survival and a lower cumulative incidence of relapse. In conclusion, NPM1 mutations represent a common genetic abnormality in adult AML. If not associated with FLT3-ITD mutations, mutant NPM1 appears to identify patients with improved response toward treatment.

Bibliography

Thiede, C., Koch, S., Creutzig, E., Steudel, C., Illmer, T., Schaich, M., & Ehninger, G. (2006). Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML). Blood, 107(10), 4011â4020.

Authors 8

Christian Thiede (first)
Sina Koch (additional)
Eva Creutzig (additional)
Christine Steudel (additional)
Thomas Illmer (additional)
Markus Schaich (additional)
Gerhard Ehninger (additional)
(additional)

References 49 Referenced 578

Dates

Type	When
Created	19 years, 7 months ago (Feb. 2, 2006, 8:58 p.m.)
Deposited	5 years, 4 months ago (April 12, 2020, 8:35 a.m.)
Indexed	4 hours, 3 minutes ago (Sept. 3, 2025, 11:43 a.m.)
Issued	19 years, 3 months ago (May 15, 2006)
Published	19 years, 3 months ago (May 15, 2006)
Published Print	19 years, 3 months ago (May 15, 2006)

Funders 0

None

BibTeX

@article{Thiede_2006, title={Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML)}, volume={107}, ISSN={1528-0020}, url={http://dx.doi.org/10.1182/blood-2005-08-3167}, DOI={10.1182/blood-2005-08-3167}, number={10}, journal={Blood}, publisher={American Society of Hematology}, author={Thiede, Christian and Koch, Sina and Creutzig, Eva and Steudel, Christine and Illmer, Thomas and Schaich, Markus and Ehninger, Gerhard}, year={2006}, month=may, pages={4011–4020} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        9,
        3
      ]
    ],
    "date-time": "2025-09-03T15:43:52Z",
    "timestamp": 1756914232533
  },
  "reference-count": 49,
  "publisher": "American Society of Hematology",
  "issue": "10",
  "content-domain": {
    "domain": [
      "ashpublications.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2006,
        5,
        15
      ]
    ]
  },
  "abstract": "<jats:p>Mutations of the nucleophosmin (NPM1) gene have recently been described in patients with acute myeloid leukemia (AML). To clarify the prevalence as well as the clinical impact of this mutation, we investigated 1485 patients with AML for NPM1 exon 12 mutations using fragment analysis. A 4 bp insert was detected in 408 of 1485 patients (27.5%). Sequence analysis revealed known mutations (type A, B, and D) as well as 13 novel alterations in 229 analyzed cases. NPM1 mutations were most prevalent in patients with normal karyotype (NK) (324 of 709; 45.7%) compared with 58 of 686 with karyotype abnormalities (8.5%; P &lt; .001) and were significantly associated with several clinical parameters (high bone marrow [BM] blasts, high white blood cell [WBC] and platelet counts, female sex). NPM1 alterations were associated with FLT3-ITD mutations, even if restricted to patients with NK (NPM1-mut/FLT3-ITD: 43.8%; versus NPM1-wt/FLT3-ITD: 19.9%; P &lt; .001). The analysis of the clinical impact in 4 groups (NPM1 and FLT3-ITD single mutants, double mutants, and wild-type [wt] for both) revealed that patients having only an NPM1 mutation had a significantly better overall and disease-free survival and a lower cumulative incidence of relapse. In conclusion, NPM1 mutations represent a common genetic abnormality in adult AML. If not associated with FLT3-ITD mutations, mutant NPM1 appears to identify patients with improved response toward treatment.</jats:p>",
  "DOI": "10.1182/blood-2005-08-3167",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2006,
        2,
        3
      ]
    ],
    "date-time": "2006-02-03T01:58:21Z",
    "timestamp": 1138931901000
  },
  "page": "4011-4020",
  "update-policy": "http://dx.doi.org/10.1182/blood.2019cm0000",
  "source": "Crossref",
  "is-referenced-by-count": 578,
  "title": "Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML)",
  "prefix": "10.1182",
  "volume": "107",
  "author": [
    {
      "given": "Christian",
      "family": "Thiede",
      "sequence": "first",
      "affiliation": [
        {
          "name": "From the Medizinische Klinik und Poliklinik I, Universita\u0308tsklinikum Carl Gustav Carus der Technischen Universita\u0308t, Dresden, Germany."
        }
      ]
    },
    {
      "given": "Sina",
      "family": "Koch",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From the Medizinische Klinik und Poliklinik I, Universita\u0308tsklinikum Carl Gustav Carus der Technischen Universita\u0308t, Dresden, Germany."
        }
      ]
    },
    {
      "given": "Eva",
      "family": "Creutzig",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From the Medizinische Klinik und Poliklinik I, Universita\u0308tsklinikum Carl Gustav Carus der Technischen Universita\u0308t, Dresden, Germany."
        }
      ]
    },
    {
      "given": "Christine",
      "family": "Steudel",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From the Medizinische Klinik und Poliklinik I, Universita\u0308tsklinikum Carl Gustav Carus der Technischen Universita\u0308t, Dresden, Germany."
        }
      ]
    },
    {
      "given": "Thomas",
      "family": "Illmer",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From the Medizinische Klinik und Poliklinik I, Universita\u0308tsklinikum Carl Gustav Carus der Technischen Universita\u0308t, Dresden, Germany."
        }
      ]
    },
    {
      "given": "Markus",
      "family": "Schaich",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From the Medizinische Klinik und Poliklinik I, Universita\u0308tsklinikum Carl Gustav Carus der Technischen Universita\u0308t, Dresden, Germany."
        }
      ]
    },
    {
      "given": "Gerhard",
      "family": "Ehninger",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From the Medizinische Klinik und Poliklinik I, Universita\u0308tsklinikum Carl Gustav Carus der Technischen Universita\u0308t, Dresden, Germany."
        }
      ]
    },
    {
      "name": "for the Deutsche Studieninitiative Leuka\u0308mie (DSIL)",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "234",
  "reference": [
    {
      "key": "2019111905592030600_REF1",
      "unstructured": "Greer JP, Baer MR, Kinney MC. Acute Myeloid Leukemia in Adults. In: Greer JP, Foerster J, Lukens JN, Rodgers GM, Paraskevas F, Glader B, eds. Wintrobe's Clinical Hematology. Philadelphia, PA: Lippincott Williams & Wilkins; 2004: 2097-2142."
    },
    {
      "key": "2019111905592030600_REF2",
      "doi-asserted-by": "crossref",
      "unstructured": "Speck NA, Gilliland DG. Core-binding factors in haematopoiesis and leukaemia. Nat Rev Cancer. 2002;2: 502-513.",
      "DOI": "10.1038/nrc840"
    },
    {
      "key": "2019111905592030600_REF3",
      "doi-asserted-by": "crossref",
      "unstructured": "Grisolano JL, O'Neal J, Cain J, Tomasson MH. An activated receptor tyrosine kinase, TEL/PDGFbetaR, cooperates with AML1/ETO to induce acute myeloid leukemia in mice. Proc Natl Acad Sci U S A. 2003;100: 9506-9511.",
      "DOI": "10.1073/pnas.1531730100"
    },
    {
      "key": "2019111905592030600_",
      "doi-asserted-by": "crossref",
      "unstructured": "Care RS, Valk PJ, Goodeve AC, et al. Incidence and prognosis of c-KIT and FLT3 mutations in core binding factor (CBF) acute myeloid leukaemias. Br J Haematol. 2003;121: 775-777.",
      "DOI": "10.1046/j.1365-2141.2003.04362.x"
    },
    {
      "key": "2019111905592030600_REF5",
      "doi-asserted-by": "crossref",
      "unstructured": "Wang YY, Zhou GB, Yin T, et al. AML1-ETO and C-KIT mutation/overexpression in t(8;21) leukemia: implication in stepwise leukemogenesis and response to Gleevec. Proc Natl Acad Sci U S A. 2005;102: 1104-1109.",
      "DOI": "10.1073/pnas.0408831102"
    },
    {
      "key": "2019111905592030600_REF6",
      "doi-asserted-by": "crossref",
      "unstructured": "Stirewalt DL, Radich JP. The role of FLT3 in haematopoietic malignancies. Nat Rev Cancer. 2003;3: 650-665.",
      "DOI": "10.1038/nrc1169"
    },
    {
      "key": "2019111905592030600_REF7",
      "unstructured": "Kiyoi H, Naoe T, Nakano Y, et al. Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. Blood. 1999;93: 3074-3080."
    },
    {
      "key": "2019111905592030600_",
      "doi-asserted-by": "crossref",
      "unstructured": "Kottaridis PD, Gale RE, Frew ME, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001;98: 1752-1759.",
      "DOI": "10.1182/blood.V98.6.1752"
    },
    {
      "key": "2019111905592030600_REF9",
      "doi-asserted-by": "crossref",
      "unstructured": "Schnittger S, Schoch C, Dugas M, et al. Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood. 2002; 100: 59-66.",
      "DOI": "10.1182/blood.V100.1.59"
    },
    {
      "key": "2019111905592030600_",
      "doi-asserted-by": "crossref",
      "unstructured": "Frohling S, Schlenk RF, Breitruck J, et al. Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm. Blood. 2002;100: 4372-4380.",
      "DOI": "10.1182/blood-2002-05-1440"
    },
    {
      "key": "2019111905592030600_REF11",
      "doi-asserted-by": "crossref",
      "unstructured": "Thiede C, Steudel C, Mohr B, et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood. 2002;99: 4326-4335.",
      "DOI": "10.1182/blood.V99.12.4326"
    },
    {
      "key": "2019111905592030600_REF12",
      "doi-asserted-by": "crossref",
      "unstructured": "Yamamoto Y, Kiyoi H, Nakano Y, et al. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood. 2001;97: 2434-2439.",
      "DOI": "10.1182/blood.V97.8.2434"
    },
    {
      "key": "2019111905592030600_REF13",
      "doi-asserted-by": "crossref",
      "unstructured": "Preudhomme C, Sagot C, Boissel N, et al. Favorable prognostic significance of CEBPA mutations in patients with de novo acute myeloid leukemia: a study from the Acute Leukemia French Association (ALFA). Blood. 2002;100: 2717-2723.",
      "DOI": "10.1182/blood-2002-03-0990"
    },
    {
      "key": "2019111905592030600_REF14",
      "doi-asserted-by": "crossref",
      "unstructured": "Frohling S, Schlenk RF, Stolze I, et al. CEBPA mutations in younger adults with acute myeloid leukemia and normal cytogenetics: prognostic relevance and analysis of cooperating mutations. J Clin Oncol. 2004;22: 624-633.",
      "DOI": "10.1200/JCO.2004.06.060"
    },
    {
      "key": "2019111905592030600_REF15",
      "doi-asserted-by": "crossref",
      "unstructured": "Falini B, Mecucci C, Tiacci E, et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med. 2005; 352: 254-266.",
      "DOI": "10.1056/NEJMoa041974"
    },
    {
      "key": "2019111905592030600_REF16",
      "doi-asserted-by": "crossref",
      "unstructured": "Borer RA, Lehner CF, Eppenberger HM, Nigg EA. Major nucleolar proteins shuttle between nucleus and cytoplasm. Cell. 1989;56: 379-390.",
      "DOI": "10.1016/0092-8674(89)90241-9"
    },
    {
      "key": "2019111905592030600_REF17",
      "doi-asserted-by": "crossref",
      "unstructured": "Dumbar TS, Gentry GA, Olson MO. Interaction of nucleolar phosphoprotein B23 with nucleic acids. Biochemistry. 1989;28: 9495-9501.",
      "DOI": "10.1021/bi00450a037"
    },
    {
      "key": "2019111905592030600_REF18",
      "doi-asserted-by": "crossref",
      "unstructured": "Tarapore P, Okuda M, Fukasawa K. A mammalian in vitro centriole duplication system: evidence for involvement of CDK2/cyclin E and nucleophosmin/B23 in centrosome duplication. Cell Cycle. 2002;1: 75-81.",
      "DOI": "10.4161/cc.1.1.103"
    },
    {
      "key": "2019111905592030600_REF19",
      "doi-asserted-by": "crossref",
      "unstructured": "Sipos K, Olson MO. Nucleolin promotes secondary structure in ribosomal RNA. Biochem Biophys Res Commun. 1991;177: 673-678.",
      "DOI": "10.1016/0006-291X(91)91841-Y"
    },
    {
      "key": "2019111905592030600_REF20",
      "doi-asserted-by": "crossref",
      "unstructured": "Colombo E, Marine JC, Danovi D, Falini B, Pelicci PG. Nucleophosmin regulates the stability and transcriptional activity of p53. Nat Cell Biol. 2002; 4: 529-533.",
      "DOI": "10.1038/ncb814"
    },
    {
      "key": "2019111905592030600_REF21",
      "doi-asserted-by": "crossref",
      "unstructured": "Takemura M, Ohoka F, Perpelescu M, et al. Phosphorylation-dependent migration of retinoblastoma protein into the nucleolus triggered by binding to nucleophosmin/B23. Exp Cell Res. 2002; 276: 233-241.",
      "DOI": "10.1006/excr.2002.5523"
    },
    {
      "key": "2019111905592030600_REF22",
      "doi-asserted-by": "crossref",
      "unstructured": "Bertwistle D, Sugimoto M, Sherr CJ. Physical and functional interactions of the Arf tumor suppressor protein with nucleophosmin/B23. Mol Cell Biol. 2004;24: 985-996.",
      "DOI": "10.1128/MCB.24.3.985-996.2004"
    },
    {
      "key": "2019111905592030600_REF23",
      "doi-asserted-by": "crossref",
      "unstructured": "Kurki S, Peltonen K, Latonen L, et al. Nucleolar protein NPM interacts with HDM2 and protects tumor suppressor protein p53 from HDM2-mediated degradation. Cancer Cell. 2004;5: 465-475.",
      "DOI": "10.1016/S1535-6108(04)00110-2"
    },
    {
      "key": "2019111905592030600_REF24",
      "doi-asserted-by": "crossref",
      "unstructured": "Li J, Zhang X, Sejas DP, Bagby GC, Pang Q. Hypoxia-induced nucleophosmin protects cell death through inhibition of p53. J Biol Chem. 2004;279: 41275-41279.",
      "DOI": "10.1074/jbc.C400297200"
    },
    {
      "key": "2019111905592030600_REF25",
      "doi-asserted-by": "crossref",
      "unstructured": "Wu MH, Yung BY. UV stimulation of nucleophosmin/B23 expression is an immediate-early gene response induced by damaged DNA. J Biol Chem. 2002;277: 48234-48240.",
      "DOI": "10.1074/jbc.M206550200"
    },
    {
      "key": "2019111905592030600_",
      "doi-asserted-by": "crossref",
      "unstructured": "Hagiwara T, Nakashima K, Hirano H, Senshu T, Yamada M. Deimination of arginine residues in nucleophosmin/B23 and histones in HL-60 granulocytes. Biochem Biophys Res Commun. 2002; 290: 979-983.",
      "DOI": "10.1006/bbrc.2001.6303"
    },
    {
      "key": "2019111905592030600_REF27",
      "doi-asserted-by": "crossref",
      "unstructured": "Wu MH, Yung BY. UV stimulation of nucleophosmin/B23 expression is an immediate-early gene response induced by damaged DNA. J Biol Chem. 2002;277: 48234-48240.",
      "DOI": "10.1074/jbc.M206550200"
    },
    {
      "key": "2019111905592030600_REF28",
      "doi-asserted-by": "crossref",
      "unstructured": "Fenaux P, Chastang C, Chevret S, et al. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group [see comments]. Blood. 1999;94: 1192-1200.",
      "DOI": "10.1182/blood.V94.4.1192"
    },
    {
      "key": "2019111905592030600_REF29",
      "doi-asserted-by": "crossref",
      "unstructured": "Schaich M, Ritter M, Illmer T, et al. Mutations in ras proto-oncogenes are associated with lower mdr1 gene expression in adult acute myeloid leukaemia. Br J Haematol. 2001;112: 300-307.",
      "DOI": "10.1046/j.1365-2141.2001.02562.x"
    },
    {
      "key": "2019111905592030600_REF30",
      "doi-asserted-by": "crossref",
      "unstructured": "Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanatephenol-chloroform extraction. Anal Biochem. 1987;162: 156-159.",
      "DOI": "10.1016/0003-2697(87)90021-2"
    },
    {
      "key": "2019111905592030600_REF31",
      "doi-asserted-by": "crossref",
      "unstructured": "Ritter M, Thiede C, Schakel U, et al. Underestimation of inversion (16) in acute myeloid leukaemia using standard cytogenetics as compared with polymerase chain reaction: results of a prospective investigation. Br J Haematol. 1997;98: 969-972.",
      "DOI": "10.1046/j.1365-2141.1997.2933107.x"
    },
    {
      "key": "2019111905592030600_REF32",
      "doi-asserted-by": "crossref",
      "unstructured": "Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53: 457-462.",
      "DOI": "10.1080/01621459.1958.10501452"
    },
    {
      "key": "2019111905592030600_REF33",
      "doi-asserted-by": "crossref",
      "unstructured": "Gray RJ. A class of k-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat. 1988;16: 1141-1154.",
      "DOI": "10.1214/aos/1176350951"
    },
    {
      "key": "2019111905592030600_REF34",
      "doi-asserted-by": "crossref",
      "unstructured": "Nishimura Y, Ohkubo T, Furuichi Y, Umekawa H. Tryptophans 286 and 288 in the C-terminal region of protein B23.1 are important for its nucleolar localization. Biosci Biotechnol Biochem. 2002;66: 2239-2242.",
      "DOI": "10.1271/bbb.66.2239"
    },
    {
      "key": "2019111905592030600_REF35",
      "doi-asserted-by": "crossref",
      "unstructured": "Suzuki T, Kiyoi H, Ozeki K, et al. Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia. Blood. 2005; 106: 2854-2861.",
      "DOI": "10.1182/blood-2005-04-1733"
    },
    {
      "key": "2019111905592030600_REF36",
      "doi-asserted-by": "crossref",
      "unstructured": "Steudel C, Wermke M, Schaich M, et al. Comparative analysis of MLL partial tandem duplication and FLT3 internal tandem duplication mutations in 956 adult patients with acute myeloid leukemia. Genes Chromosomes Cancer. 2003; 37: 237-251.",
      "DOI": "10.1002/gcc.10219"
    },
    {
      "key": "2019111905592030600_REF37",
      "unstructured": "Whitman SP, Archer KJ, Feng L, et al. Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a cancer and leukemia group B study. Cancer Res. 2001;61: 7233-7239."
    },
    {
      "key": "2019111905592030600_REF38",
      "doi-asserted-by": "crossref",
      "unstructured": "Boissel N, Renneville A, Biggio V, et al. Prevalence, clinical profile and prognosis of NPM mutations in AML with normal karyotype. Blood. 2005; 106: 3618-3620.",
      "DOI": "10.1182/blood-2005-05-2174"
    },
    {
      "key": "2019111905592030600_REF39",
      "doi-asserted-by": "crossref",
      "unstructured": "Noguera NI, Ammatuna E, Zangrilli D, et al. Simultaneous detection of NPM1 and FLT3-ITD mutations by capillary electrophoresis in acute myeloid leukemia. Leukemia. 2005;19: 1479-1482.",
      "DOI": "10.1038/sj.leu.2403846"
    },
    {
      "key": "2019111905592030600_REF40",
      "doi-asserted-by": "crossref",
      "unstructured": "Cazzaniga G, Dell'oro MG, Mecucci C, et al. Nucleophosmin mutations in childhood acute myelogenous leukemia with normal karyotype. Blood. 2005;106: 1419-1422.",
      "DOI": "10.1182/blood-2005-03-0899"
    },
    {
      "key": "2019111905592030600_REF41",
      "doi-asserted-by": "crossref",
      "unstructured": "Hsu CY, Yung BY. Involvement of nucleophosmin/B23 in TPA-induced megakaryocytic differentiation of K562 cells. Br J Cancer. 2003;89: 1320-1326.",
      "DOI": "10.1038/sj.bjc.6601100"
    },
    {
      "key": "2019111905592030600_REF42",
      "doi-asserted-by": "crossref",
      "unstructured": "Li J, Zhang X, Sejas DP, Pang Q. Negative regulation of p53 by nucleophosmin antagonizes stress-induced apoptosis in human normal and malignant hematopoietic cells. Leuk Res. 2005; 29: 1415-1423.",
      "DOI": "10.1016/j.leukres.2005.05.005"
    },
    {
      "key": "2019111905592030600_REF43",
      "doi-asserted-by": "crossref",
      "unstructured": "Maiguel DA, Jones L, Chakravarty D, Yang C, Carrier F. Nucleophosmin sets a threshold for p53 response to UV radiation. Mol Cell Biol. 2004;24: 3703-3711.",
      "DOI": "10.1128/MCB.24.9.3703-3711.2004"
    },
    {
      "key": "2019111905592030600_REF44",
      "doi-asserted-by": "crossref",
      "unstructured": "Choudhary C, Schwable J, Brandts C, et al. AML-associated Flt3 kinase domain mutations show signal transduction differences compared with Flt3 ITD mutations. Blood. 2005;106: 265-273.",
      "DOI": "10.1182/blood-2004-07-2942"
    },
    {
      "key": "2019111905592030600_REF45",
      "doi-asserted-by": "crossref",
      "unstructured": "Grisendi S, Bernardi R, Rossi M, et al. Role of nucleophosmin in embryonic development and tumorigenesis. Nature. 2005;437: 147-153.",
      "DOI": "10.1038/nature03915"
    },
    {
      "key": "2019111905592030600_REF46",
      "doi-asserted-by": "crossref",
      "unstructured": "Grundler R, Miething C, Thiede C, Peschel C, Duyster J. FLT3-ITD and tyrosine kinase domain mutants induce two distinct phenotypes in a murine bone marrow transplantation model. Blood. 2005;105: 4792-4799.",
      "DOI": "10.1182/blood-2004-11-4430"
    },
    {
      "key": "2019111905592030600_REF47",
      "doi-asserted-by": "crossref",
      "unstructured": "Verhaak RG, Goudswaard CS, van Putten W, et al. Mutations in nucleophosmin (NPM1) in acute myeloid leukemia (AML): association with other gene abnormalities and previously established gene expression signatures and their favorable prognostic significance. Blood. 2005;106: 3747-3754.",
      "DOI": "10.1182/blood-2005-05-2168"
    },
    {
      "key": "2019111905592030600_",
      "doi-asserted-by": "crossref",
      "unstructured": "Schnittger S, Schoch C, Kern W, et al. Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype. Blood. 2005;106: 3733-3739.",
      "DOI": "10.1182/blood-2005-06-2248"
    },
    {
      "key": "2019111905592030600_REF49",
      "doi-asserted-by": "crossref",
      "unstructured": "Dohner K, Schlenk RF, Habdank M, et al. Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood. 2005;106: 3740-3746.",
      "DOI": "10.1182/blood-2005-05-2164"
    }
  ],
  "container-title": "Blood",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "http://ashpublications.org/blood/article-pdf/107/10/4011/466128/zh801006004011.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "http://ashpublications.org/blood/article-pdf/107/10/4011/466128/zh801006004011.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2020,
        4,
        12
      ]
    ],
    "date-time": "2020-04-12T12:35:20Z",
    "timestamp": 1586694920000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://ashpublications.org/blood/article/107/10/4011/109773/Prevalence-and-prognostic-impact-of-NPM1-mutations"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2006,
        5,
        15
      ]
    ]
  },
  "references-count": 49,
  "journal-issue": {
    "issue": "10",
    "published-print": {
      "date-parts": [
        [
          2006,
          5,
          15
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1182/blood-2005-08-3167",
  "relation": {},
  "ISSN": [
    "0006-4971",
    "1528-0020"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        2006,
        5,
        15
      ]
    ]
  }
}