Cytoplasmic localization of nucleophosmin in bone marrow blasts of acute myeloid leukemia patients is not completely concordant with NPM1 mutation and is not predictive of prognosis

Sergej Konoplev, Huang Xuelin, Harry A. Drabkin, Hartmut Koeppen, Dan Jones, Hagop M. Kantarjian, Guillermo Garcia-Manero, Chen Weina, L. Jeffrey Medeiros, Carlos E. Bueso-Ramos

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Abstract

BACKGROUND: Nucleophosmin (NPM1) gene mutations are reported to predict a favorable prognosis in acute myeloid leukemia (AML) patients. Aberrant cytoplasmic localization of nucleophosmin (NPM) protein is reported be a surrogate for NPM1 gene mutation. METHODS: Using immunohistochemical (IHC) analysis, we assessed for NPM (clone 376) expression in formalin-fixed, formic acid-decalcified bone marrow biopsy specimens. DNA sequencing of exon 12 of NPM1 gene was performed in 104 patients. RESULTS: The study included 252 AML patients: 192 de novo AML, 33 AML preceded by either myelodysplastic syndrome or chronic myelomonocytic leukemia, and 27 therapy-related AML. The median age was 62 years and 115 patients were ≤60 years old. All patients received intensive chemotherapy. Cytoplasmic NPM was detected in 59 of 252 (23%) patients, including 48 of 192 (25%) de novo AML and 33 of 94 (35%) with a normal karyotype. DNA sequencing identified NPM1 mutations in 30 of 38 cases with cytoplasmic NPM and 10 of 66 cases with nuclear NPM. Cytoplasmic NPM was associated with young patient age (P = .024), FLT3/ITD (P = .005), CD34 negative blasts (P < .001), high peripheral blood blast count (P = .041), and high serum albumin level (P = .028). No statistical differences in overall or event-free survival were found on the basis of NPM localization. Similar results were obtained in patients ≤60 years old with normal karyotype and wild-type FLT3 (P = .768). CONCLUSIONS: IHC assessment for NPM localization did not predict prognosis in this patient cohort. The discordance between immunohistochemistry and DNA sequencing results indicates that DNA sequencing cannot be replaced by IHC assessment.

Original languageEnglish (US)
Pages (from-to)4737-4744
Number of pages8
JournalCancer
Volume115
Issue number20
DOIs
StatePublished - Oct 15 2009

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Acute Myeloid Leukemia
Bone Marrow
Mutation
DNA Sequence Analysis
formic acid
Karyotype
Leukemia, Myelomonocytic, Chronic
Genes
nucleophosmin
Myelodysplastic Syndromes
Serum Albumin
Formaldehyde
Disease-Free Survival
Exons
Clone Cells
Immunohistochemistry
Biopsy
Drug Therapy

Keywords

  • AML
  • FLT3/ITD
  • Immunohistochemical analysis
  • NPM1 mutation
  • Prognosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cytoplasmic localization of nucleophosmin in bone marrow blasts of acute myeloid leukemia patients is not completely concordant with NPM1 mutation and is not predictive of prognosis. / Konoplev, Sergej; Xuelin, Huang; Drabkin, Harry A.; Koeppen, Hartmut; Jones, Dan; Kantarjian, Hagop M.; Garcia-Manero, Guillermo; Weina, Chen; Medeiros, L. Jeffrey; Bueso-Ramos, Carlos E.

In: Cancer, Vol. 115, No. 20, 15.10.2009, p. 4737-4744.

Research output: Contribution to journalArticle

Konoplev, S, Xuelin, H, Drabkin, HA, Koeppen, H, Jones, D, Kantarjian, HM, Garcia-Manero, G, Weina, C, Medeiros, LJ & Bueso-Ramos, CE 2009, 'Cytoplasmic localization of nucleophosmin in bone marrow blasts of acute myeloid leukemia patients is not completely concordant with NPM1 mutation and is not predictive of prognosis', Cancer, vol. 115, no. 20, pp. 4737-4744. https://doi.org/10.1002/cncr.24543
Konoplev, Sergej ; Xuelin, Huang ; Drabkin, Harry A. ; Koeppen, Hartmut ; Jones, Dan ; Kantarjian, Hagop M. ; Garcia-Manero, Guillermo ; Weina, Chen ; Medeiros, L. Jeffrey ; Bueso-Ramos, Carlos E. / Cytoplasmic localization of nucleophosmin in bone marrow blasts of acute myeloid leukemia patients is not completely concordant with NPM1 mutation and is not predictive of prognosis. In: Cancer. 2009 ; Vol. 115, No. 20. pp. 4737-4744.
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abstract = "BACKGROUND: Nucleophosmin (NPM1) gene mutations are reported to predict a favorable prognosis in acute myeloid leukemia (AML) patients. Aberrant cytoplasmic localization of nucleophosmin (NPM) protein is reported be a surrogate for NPM1 gene mutation. METHODS: Using immunohistochemical (IHC) analysis, we assessed for NPM (clone 376) expression in formalin-fixed, formic acid-decalcified bone marrow biopsy specimens. DNA sequencing of exon 12 of NPM1 gene was performed in 104 patients. RESULTS: The study included 252 AML patients: 192 de novo AML, 33 AML preceded by either myelodysplastic syndrome or chronic myelomonocytic leukemia, and 27 therapy-related AML. The median age was 62 years and 115 patients were ≤60 years old. All patients received intensive chemotherapy. Cytoplasmic NPM was detected in 59 of 252 (23{\%}) patients, including 48 of 192 (25{\%}) de novo AML and 33 of 94 (35{\%}) with a normal karyotype. DNA sequencing identified NPM1 mutations in 30 of 38 cases with cytoplasmic NPM and 10 of 66 cases with nuclear NPM. Cytoplasmic NPM was associated with young patient age (P = .024), FLT3/ITD (P = .005), CD34 negative blasts (P < .001), high peripheral blood blast count (P = .041), and high serum albumin level (P = .028). No statistical differences in overall or event-free survival were found on the basis of NPM localization. Similar results were obtained in patients ≤60 years old with normal karyotype and wild-type FLT3 (P = .768). CONCLUSIONS: IHC assessment for NPM localization did not predict prognosis in this patient cohort. The discordance between immunohistochemistry and DNA sequencing results indicates that DNA sequencing cannot be replaced by IHC assessment.",
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author = "Sergej Konoplev and Huang Xuelin and Drabkin, {Harry A.} and Hartmut Koeppen and Dan Jones and Kantarjian, {Hagop M.} and Guillermo Garcia-Manero and Chen Weina and Medeiros, {L. Jeffrey} and Bueso-Ramos, {Carlos E.}",
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T1 - Cytoplasmic localization of nucleophosmin in bone marrow blasts of acute myeloid leukemia patients is not completely concordant with NPM1 mutation and is not predictive of prognosis

AU - Konoplev, Sergej

AU - Xuelin, Huang

AU - Drabkin, Harry A.

AU - Koeppen, Hartmut

AU - Jones, Dan

AU - Kantarjian, Hagop M.

AU - Garcia-Manero, Guillermo

AU - Weina, Chen

AU - Medeiros, L. Jeffrey

AU - Bueso-Ramos, Carlos E.

PY - 2009/10/15

Y1 - 2009/10/15

N2 - BACKGROUND: Nucleophosmin (NPM1) gene mutations are reported to predict a favorable prognosis in acute myeloid leukemia (AML) patients. Aberrant cytoplasmic localization of nucleophosmin (NPM) protein is reported be a surrogate for NPM1 gene mutation. METHODS: Using immunohistochemical (IHC) analysis, we assessed for NPM (clone 376) expression in formalin-fixed, formic acid-decalcified bone marrow biopsy specimens. DNA sequencing of exon 12 of NPM1 gene was performed in 104 patients. RESULTS: The study included 252 AML patients: 192 de novo AML, 33 AML preceded by either myelodysplastic syndrome or chronic myelomonocytic leukemia, and 27 therapy-related AML. The median age was 62 years and 115 patients were ≤60 years old. All patients received intensive chemotherapy. Cytoplasmic NPM was detected in 59 of 252 (23%) patients, including 48 of 192 (25%) de novo AML and 33 of 94 (35%) with a normal karyotype. DNA sequencing identified NPM1 mutations in 30 of 38 cases with cytoplasmic NPM and 10 of 66 cases with nuclear NPM. Cytoplasmic NPM was associated with young patient age (P = .024), FLT3/ITD (P = .005), CD34 negative blasts (P < .001), high peripheral blood blast count (P = .041), and high serum albumin level (P = .028). No statistical differences in overall or event-free survival were found on the basis of NPM localization. Similar results were obtained in patients ≤60 years old with normal karyotype and wild-type FLT3 (P = .768). CONCLUSIONS: IHC assessment for NPM localization did not predict prognosis in this patient cohort. The discordance between immunohistochemistry and DNA sequencing results indicates that DNA sequencing cannot be replaced by IHC assessment.

AB - BACKGROUND: Nucleophosmin (NPM1) gene mutations are reported to predict a favorable prognosis in acute myeloid leukemia (AML) patients. Aberrant cytoplasmic localization of nucleophosmin (NPM) protein is reported be a surrogate for NPM1 gene mutation. METHODS: Using immunohistochemical (IHC) analysis, we assessed for NPM (clone 376) expression in formalin-fixed, formic acid-decalcified bone marrow biopsy specimens. DNA sequencing of exon 12 of NPM1 gene was performed in 104 patients. RESULTS: The study included 252 AML patients: 192 de novo AML, 33 AML preceded by either myelodysplastic syndrome or chronic myelomonocytic leukemia, and 27 therapy-related AML. The median age was 62 years and 115 patients were ≤60 years old. All patients received intensive chemotherapy. Cytoplasmic NPM was detected in 59 of 252 (23%) patients, including 48 of 192 (25%) de novo AML and 33 of 94 (35%) with a normal karyotype. DNA sequencing identified NPM1 mutations in 30 of 38 cases with cytoplasmic NPM and 10 of 66 cases with nuclear NPM. Cytoplasmic NPM was associated with young patient age (P = .024), FLT3/ITD (P = .005), CD34 negative blasts (P < .001), high peripheral blood blast count (P = .041), and high serum albumin level (P = .028). No statistical differences in overall or event-free survival were found on the basis of NPM localization. Similar results were obtained in patients ≤60 years old with normal karyotype and wild-type FLT3 (P = .768). CONCLUSIONS: IHC assessment for NPM localization did not predict prognosis in this patient cohort. The discordance between immunohistochemistry and DNA sequencing results indicates that DNA sequencing cannot be replaced by IHC assessment.

KW - AML

KW - FLT3/ITD

KW - Immunohistochemical analysis

KW - NPM1 mutation

KW - Prognosis

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