TY - JOUR
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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U2 - 10.1002/cncr.24543
DO - 10.1002/cncr.24543
M3 - Article
C2 - 19637342
AN - SCOPUS:70350091450
SN - 0008-543X
VL - 115
SP - 4737
EP - 4744
JO - Cancer
JF - Cancer
IS - 20
ER -