Cuplike nuclei (prominent nuclear invaginations) in acute myeloid leukemia are highly associated with FLT3 internal tandem duplication and NPM1 mutation

Weina Chen, Sergej Konoplev, L. Jeffrey Medeiros, Hartmut Koeppen, Vasiliki Leventaki, Saroj Vadhan-Raj, Dan Jones, Hagop M. Kantarjian, Brunangelo Falini, Carlos E. Bueso-Ramos

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Abstract

BACKGROUND: A small subset of patients with acute myeloid leukemia (AML) have cuplike nuclei. Other investigators have demonstrated that these neoplasms have distinctive clinicopathologic and molecular features. METHODS: The authors searched for patients who had AML with cuplike nuclei at their institution over a 10-year interval. A strict definition for cuplike nuclei was used: ≥10% blasts with nuclear invaginations in ≥25% of the nuclear area. The relevant data were reviewed, and the results were compared with a control group of patients who had AML without cuplike nuclei. RESULTS: In total, 22 patients who had AML with cuplike nuclei were identified and were classified as AML without maturation (French-American-British classification M1) (AML M1). Compared with the control group (AML M1), patients who had AML with cuplike nuclei were associated significantly with fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) (86% vs 38%, respectively; P=.002); nucleophosmin 1 (NPM1) mutations (86% vs 19%; P < .0001); both mutations (77% vs 14%; P < .0001); normal karyotype (86% vs 40%; P=.003); bone marrow blast count (90% vs 84%; P=.016); myeloperoxidase positivity (95% vs 30% blasts; P=.001); higher D-dimer levels (>5000 ng/mL vs 569 ng/mL; P=.001); and the absence of CD7 (91% vs 52%; P=.007), CD34 (82% vs 5%; P < .0001), and human leukocyte antigen, D-related (59% vs 10%; P=.001). There were no differences in age, sex, or peripheral blood counts. The positive predictive value of recognizing AML with cuplike nuclei for FLT3-ITD, NPM1, and both mutations was 81%, 86%, and 77%, respectively. CONCLUSIONS: Cuplike nuclei in AML were highly associated with the presence of NPM1 and FLT3-ITD mutations and with several clinicopathologic and immunophenotypic features. Recognition of the distinctive morphologic features of AML with cuplike nuclei may be helpful in streamlining the workup of these neoplasms.

Original languageEnglish (US)
Pages (from-to)5481-5489
Number of pages9
JournalCancer
Volume115
Issue number23
DOIs
StatePublished - Jan 12 2009

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fms-Like Tyrosine Kinase 3
Acute Myeloid Leukemia
Mutation
nucleophosmin
Control Groups
HLA Antigens
Neoplasms

Keywords

  • Acute myeloid leukemia
  • Cuplike nuclear morphology
  • Cytogenetics
  • Fms-like tyrosine kinase 3 mutations
  • Immunophenotype
  • Nucleophosmin 1 mutations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cuplike nuclei (prominent nuclear invaginations) in acute myeloid leukemia are highly associated with FLT3 internal tandem duplication and NPM1 mutation. / Chen, Weina; Konoplev, Sergej; Medeiros, L. Jeffrey; Koeppen, Hartmut; Leventaki, Vasiliki; Vadhan-Raj, Saroj; Jones, Dan; Kantarjian, Hagop M.; Falini, Brunangelo; Bueso-Ramos, Carlos E.

In: Cancer, Vol. 115, No. 23, 12.01.2009, p. 5481-5489.

Research output: Contribution to journalArticle

Chen, W, Konoplev, S, Medeiros, LJ, Koeppen, H, Leventaki, V, Vadhan-Raj, S, Jones, D, Kantarjian, HM, Falini, B & Bueso-Ramos, CE 2009, 'Cuplike nuclei (prominent nuclear invaginations) in acute myeloid leukemia are highly associated with FLT3 internal tandem duplication and NPM1 mutation', Cancer, vol. 115, no. 23, pp. 5481-5489. https://doi.org/10.1002/cncr.24610
Chen, Weina ; Konoplev, Sergej ; Medeiros, L. Jeffrey ; Koeppen, Hartmut ; Leventaki, Vasiliki ; Vadhan-Raj, Saroj ; Jones, Dan ; Kantarjian, Hagop M. ; Falini, Brunangelo ; Bueso-Ramos, Carlos E. / Cuplike nuclei (prominent nuclear invaginations) in acute myeloid leukemia are highly associated with FLT3 internal tandem duplication and NPM1 mutation. In: Cancer. 2009 ; Vol. 115, No. 23. pp. 5481-5489.
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title = "Cuplike nuclei (prominent nuclear invaginations) in acute myeloid leukemia are highly associated with FLT3 internal tandem duplication and NPM1 mutation",
abstract = "BACKGROUND: A small subset of patients with acute myeloid leukemia (AML) have cuplike nuclei. Other investigators have demonstrated that these neoplasms have distinctive clinicopathologic and molecular features. METHODS: The authors searched for patients who had AML with cuplike nuclei at their institution over a 10-year interval. A strict definition for cuplike nuclei was used: ≥10{\%} blasts with nuclear invaginations in ≥25{\%} of the nuclear area. The relevant data were reviewed, and the results were compared with a control group of patients who had AML without cuplike nuclei. RESULTS: In total, 22 patients who had AML with cuplike nuclei were identified and were classified as AML without maturation (French-American-British classification M1) (AML M1). Compared with the control group (AML M1), patients who had AML with cuplike nuclei were associated significantly with fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) (86{\%} vs 38{\%}, respectively; P=.002); nucleophosmin 1 (NPM1) mutations (86{\%} vs 19{\%}; P < .0001); both mutations (77{\%} vs 14{\%}; P < .0001); normal karyotype (86{\%} vs 40{\%}; P=.003); bone marrow blast count (90{\%} vs 84{\%}; P=.016); myeloperoxidase positivity (95{\%} vs 30{\%} blasts; P=.001); higher D-dimer levels (>5000 ng/mL vs 569 ng/mL; P=.001); and the absence of CD7 (91{\%} vs 52{\%}; P=.007), CD34 (82{\%} vs 5{\%}; P < .0001), and human leukocyte antigen, D-related (59{\%} vs 10{\%}; P=.001). There were no differences in age, sex, or peripheral blood counts. The positive predictive value of recognizing AML with cuplike nuclei for FLT3-ITD, NPM1, and both mutations was 81{\%}, 86{\%}, and 77{\%}, respectively. CONCLUSIONS: Cuplike nuclei in AML were highly associated with the presence of NPM1 and FLT3-ITD mutations and with several clinicopathologic and immunophenotypic features. Recognition of the distinctive morphologic features of AML with cuplike nuclei may be helpful in streamlining the workup of these neoplasms.",
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author = "Weina Chen and Sergej Konoplev and Medeiros, {L. Jeffrey} and Hartmut Koeppen and Vasiliki Leventaki and Saroj Vadhan-Raj and Dan Jones and Kantarjian, {Hagop M.} and Brunangelo Falini and Bueso-Ramos, {Carlos E.}",
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T1 - Cuplike nuclei (prominent nuclear invaginations) in acute myeloid leukemia are highly associated with FLT3 internal tandem duplication and NPM1 mutation

AU - Chen, Weina

AU - Konoplev, Sergej

AU - Medeiros, L. Jeffrey

AU - Koeppen, Hartmut

AU - Leventaki, Vasiliki

AU - Vadhan-Raj, Saroj

AU - Jones, Dan

AU - Kantarjian, Hagop M.

AU - Falini, Brunangelo

AU - Bueso-Ramos, Carlos E.

PY - 2009/1/12

Y1 - 2009/1/12

N2 - BACKGROUND: A small subset of patients with acute myeloid leukemia (AML) have cuplike nuclei. Other investigators have demonstrated that these neoplasms have distinctive clinicopathologic and molecular features. METHODS: The authors searched for patients who had AML with cuplike nuclei at their institution over a 10-year interval. A strict definition for cuplike nuclei was used: ≥10% blasts with nuclear invaginations in ≥25% of the nuclear area. The relevant data were reviewed, and the results were compared with a control group of patients who had AML without cuplike nuclei. RESULTS: In total, 22 patients who had AML with cuplike nuclei were identified and were classified as AML without maturation (French-American-British classification M1) (AML M1). Compared with the control group (AML M1), patients who had AML with cuplike nuclei were associated significantly with fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) (86% vs 38%, respectively; P=.002); nucleophosmin 1 (NPM1) mutations (86% vs 19%; P < .0001); both mutations (77% vs 14%; P < .0001); normal karyotype (86% vs 40%; P=.003); bone marrow blast count (90% vs 84%; P=.016); myeloperoxidase positivity (95% vs 30% blasts; P=.001); higher D-dimer levels (>5000 ng/mL vs 569 ng/mL; P=.001); and the absence of CD7 (91% vs 52%; P=.007), CD34 (82% vs 5%; P < .0001), and human leukocyte antigen, D-related (59% vs 10%; P=.001). There were no differences in age, sex, or peripheral blood counts. The positive predictive value of recognizing AML with cuplike nuclei for FLT3-ITD, NPM1, and both mutations was 81%, 86%, and 77%, respectively. CONCLUSIONS: Cuplike nuclei in AML were highly associated with the presence of NPM1 and FLT3-ITD mutations and with several clinicopathologic and immunophenotypic features. Recognition of the distinctive morphologic features of AML with cuplike nuclei may be helpful in streamlining the workup of these neoplasms.

AB - BACKGROUND: A small subset of patients with acute myeloid leukemia (AML) have cuplike nuclei. Other investigators have demonstrated that these neoplasms have distinctive clinicopathologic and molecular features. METHODS: The authors searched for patients who had AML with cuplike nuclei at their institution over a 10-year interval. A strict definition for cuplike nuclei was used: ≥10% blasts with nuclear invaginations in ≥25% of the nuclear area. The relevant data were reviewed, and the results were compared with a control group of patients who had AML without cuplike nuclei. RESULTS: In total, 22 patients who had AML with cuplike nuclei were identified and were classified as AML without maturation (French-American-British classification M1) (AML M1). Compared with the control group (AML M1), patients who had AML with cuplike nuclei were associated significantly with fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) (86% vs 38%, respectively; P=.002); nucleophosmin 1 (NPM1) mutations (86% vs 19%; P < .0001); both mutations (77% vs 14%; P < .0001); normal karyotype (86% vs 40%; P=.003); bone marrow blast count (90% vs 84%; P=.016); myeloperoxidase positivity (95% vs 30% blasts; P=.001); higher D-dimer levels (>5000 ng/mL vs 569 ng/mL; P=.001); and the absence of CD7 (91% vs 52%; P=.007), CD34 (82% vs 5%; P < .0001), and human leukocyte antigen, D-related (59% vs 10%; P=.001). There were no differences in age, sex, or peripheral blood counts. The positive predictive value of recognizing AML with cuplike nuclei for FLT3-ITD, NPM1, and both mutations was 81%, 86%, and 77%, respectively. CONCLUSIONS: Cuplike nuclei in AML were highly associated with the presence of NPM1 and FLT3-ITD mutations and with several clinicopathologic and immunophenotypic features. Recognition of the distinctive morphologic features of AML with cuplike nuclei may be helpful in streamlining the workup of these neoplasms.

KW - Acute myeloid leukemia

KW - Cuplike nuclear morphology

KW - Cytogenetics

KW - Fms-like tyrosine kinase 3 mutations

KW - Immunophenotype

KW - Nucleophosmin 1 mutations

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