A simple cytofluorimetric score may optimize testing for biallelic CEBPA mutations in patients with acute myeloid leukemia

Riccardo Marcolin, Fabio Guolo, Paola Minetto, Marino Clavio, Lorenzo Manconi, Filippo Ballerini, Alessandro Carli, Monica Passannante, Nicoletta Colombo, Enrico Carminati, Girolamo Pugliese, Elisabetta Tedone, Paola Contini, Rosa Mangerini, Annalisa Kunkl, Maurizio Miglino, Antonia Cagnetta, Michele Cea, Marco Gobbi, Roberto Massimo Lemoli

Research output: Contribution to journalArticle

Abstract

Acute myeloid leukemia with biallelic mutation of CEBPA (CEBPA-dm AML) is a distinct good prognosis entity recognized by WHO 2016 classification. However, testing for CEBPA mutation is challenging, due to the intrinsic characteristics of the mutation itself. Indeed, molecular analysis cannot be performed with NGS technique and requires Sanger sequencing. The association of recurrent mutations or translocations with specific immunophenotypic patterns has been already reported in other AML subtypes. The aim of this study was the development of a specific cytofluorimetric score (CEBPA-dm score), in order to distinguish patients who are unlikely to harbor the mutation. To this end, the correlation of CEBPA-dm score with the presence of the mutation was analyzed in 50 consecutive AML patients with normal karyotype and without NPM1 mutation (that is mutually exclusive with CEBPA mutation). One point each was assigned for expression of HLA DR, CD7, CD13, CD15, CD33, CD34 and one point for lack of expression of CD14. OS was not influenced by sex, age and CEBPA-dm score. Multivariate OS analysis showed that CEBPA-dm (p < 0.02) and FLT3-ITD (p < 0.01) were the strongest independent predictors of OS. With a high negative predictive value (100%), CEBPA-dm score < 6 was able to identify patients who are unlikely to have the mutation. Therefore, the application of this simple score might optimize the use of expensive and time-consuming diagnostic and prognostic assessment in the baseline work up of AML patients.

Original languageEnglish
Article number106223
JournalLeukemia Research
Volume86
DOIs
Publication statusPublished - Nov 1 2019

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Acute Myeloid Leukemia
Mutation
HLA-DR Antigens
Karyotype
Multivariate Analysis

Keywords

  • Acute myeloid leukemia
  • CEBPA
  • Immunophenotype

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

A simple cytofluorimetric score may optimize testing for biallelic CEBPA mutations in patients with acute myeloid leukemia. / Marcolin, Riccardo; Guolo, Fabio; Minetto, Paola; Clavio, Marino; Manconi, Lorenzo; Ballerini, Filippo; Carli, Alessandro; Passannante, Monica; Colombo, Nicoletta; Carminati, Enrico; Pugliese, Girolamo; Tedone, Elisabetta; Contini, Paola; Mangerini, Rosa; Kunkl, Annalisa; Miglino, Maurizio; Cagnetta, Antonia; Cea, Michele; Gobbi, Marco; Lemoli, Roberto Massimo.

In: Leukemia Research, Vol. 86, 106223, 01.11.2019.

Research output: Contribution to journalArticle

Marcolin, R, Guolo, F, Minetto, P, Clavio, M, Manconi, L, Ballerini, F, Carli, A, Passannante, M, Colombo, N, Carminati, E, Pugliese, G, Tedone, E, Contini, P, Mangerini, R, Kunkl, A, Miglino, M, Cagnetta, A, Cea, M, Gobbi, M & Lemoli, RM 2019, 'A simple cytofluorimetric score may optimize testing for biallelic CEBPA mutations in patients with acute myeloid leukemia', Leukemia Research, vol. 86, 106223. https://doi.org/10.1016/j.leukres.2019.106223
Marcolin, Riccardo ; Guolo, Fabio ; Minetto, Paola ; Clavio, Marino ; Manconi, Lorenzo ; Ballerini, Filippo ; Carli, Alessandro ; Passannante, Monica ; Colombo, Nicoletta ; Carminati, Enrico ; Pugliese, Girolamo ; Tedone, Elisabetta ; Contini, Paola ; Mangerini, Rosa ; Kunkl, Annalisa ; Miglino, Maurizio ; Cagnetta, Antonia ; Cea, Michele ; Gobbi, Marco ; Lemoli, Roberto Massimo. / A simple cytofluorimetric score may optimize testing for biallelic CEBPA mutations in patients with acute myeloid leukemia. In: Leukemia Research. 2019 ; Vol. 86.
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abstract = "Acute myeloid leukemia with biallelic mutation of CEBPA (CEBPA-dm AML) is a distinct good prognosis entity recognized by WHO 2016 classification. However, testing for CEBPA mutation is challenging, due to the intrinsic characteristics of the mutation itself. Indeed, molecular analysis cannot be performed with NGS technique and requires Sanger sequencing. The association of recurrent mutations or translocations with specific immunophenotypic patterns has been already reported in other AML subtypes. The aim of this study was the development of a specific cytofluorimetric score (CEBPA-dm score), in order to distinguish patients who are unlikely to harbor the mutation. To this end, the correlation of CEBPA-dm score with the presence of the mutation was analyzed in 50 consecutive AML patients with normal karyotype and without NPM1 mutation (that is mutually exclusive with CEBPA mutation). One point each was assigned for expression of HLA DR, CD7, CD13, CD15, CD33, CD34 and one point for lack of expression of CD14. OS was not influenced by sex, age and CEBPA-dm score. Multivariate OS analysis showed that CEBPA-dm (p < 0.02) and FLT3-ITD (p < 0.01) were the strongest independent predictors of OS. With a high negative predictive value (100{\%}), CEBPA-dm score < 6 was able to identify patients who are unlikely to have the mutation. Therefore, the application of this simple score might optimize the use of expensive and time-consuming diagnostic and prognostic assessment in the baseline work up of AML patients.",
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AU - Marcolin, Riccardo

AU - Guolo, Fabio

AU - Minetto, Paola

AU - Clavio, Marino

AU - Manconi, Lorenzo

AU - Ballerini, Filippo

AU - Carli, Alessandro

AU - Passannante, Monica

AU - Colombo, Nicoletta

AU - Carminati, Enrico

AU - Pugliese, Girolamo

AU - Tedone, Elisabetta

AU - Contini, Paola

AU - Mangerini, Rosa

AU - Kunkl, Annalisa

AU - Miglino, Maurizio

AU - Cagnetta, Antonia

AU - Cea, Michele

AU - Gobbi, Marco

AU - Lemoli, Roberto Massimo

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Acute myeloid leukemia with biallelic mutation of CEBPA (CEBPA-dm AML) is a distinct good prognosis entity recognized by WHO 2016 classification. However, testing for CEBPA mutation is challenging, due to the intrinsic characteristics of the mutation itself. Indeed, molecular analysis cannot be performed with NGS technique and requires Sanger sequencing. The association of recurrent mutations or translocations with specific immunophenotypic patterns has been already reported in other AML subtypes. The aim of this study was the development of a specific cytofluorimetric score (CEBPA-dm score), in order to distinguish patients who are unlikely to harbor the mutation. To this end, the correlation of CEBPA-dm score with the presence of the mutation was analyzed in 50 consecutive AML patients with normal karyotype and without NPM1 mutation (that is mutually exclusive with CEBPA mutation). One point each was assigned for expression of HLA DR, CD7, CD13, CD15, CD33, CD34 and one point for lack of expression of CD14. OS was not influenced by sex, age and CEBPA-dm score. Multivariate OS analysis showed that CEBPA-dm (p < 0.02) and FLT3-ITD (p < 0.01) were the strongest independent predictors of OS. With a high negative predictive value (100%), CEBPA-dm score < 6 was able to identify patients who are unlikely to have the mutation. Therefore, the application of this simple score might optimize the use of expensive and time-consuming diagnostic and prognostic assessment in the baseline work up of AML patients.

AB - Acute myeloid leukemia with biallelic mutation of CEBPA (CEBPA-dm AML) is a distinct good prognosis entity recognized by WHO 2016 classification. However, testing for CEBPA mutation is challenging, due to the intrinsic characteristics of the mutation itself. Indeed, molecular analysis cannot be performed with NGS technique and requires Sanger sequencing. The association of recurrent mutations or translocations with specific immunophenotypic patterns has been already reported in other AML subtypes. The aim of this study was the development of a specific cytofluorimetric score (CEBPA-dm score), in order to distinguish patients who are unlikely to harbor the mutation. To this end, the correlation of CEBPA-dm score with the presence of the mutation was analyzed in 50 consecutive AML patients with normal karyotype and without NPM1 mutation (that is mutually exclusive with CEBPA mutation). One point each was assigned for expression of HLA DR, CD7, CD13, CD15, CD33, CD34 and one point for lack of expression of CD14. OS was not influenced by sex, age and CEBPA-dm score. Multivariate OS analysis showed that CEBPA-dm (p < 0.02) and FLT3-ITD (p < 0.01) were the strongest independent predictors of OS. With a high negative predictive value (100%), CEBPA-dm score < 6 was able to identify patients who are unlikely to have the mutation. Therefore, the application of this simple score might optimize the use of expensive and time-consuming diagnostic and prognostic assessment in the baseline work up of AML patients.

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KW - Immunophenotype

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