WT1 overexpression at diagnosis may predict favorable outcome in patients with de novo non-M3 acute myeloid leukemia

Maurizio Miglino, Nicoletta Colombo, Gianmatteo Pica, Raffaella Grasso, Marino Clavio, Micaela Bergamaschi, Filippo Ballerini, Anna Ghiso, Chiara Ghiggi, Laura Mitscheunig, Germana Beltrami, Antonia Cagnetta, Luana Vignolo, Maria Vita Lucchetti, Sara Aquino, Ivana Pierri, Mario Sessarego, Angelo Michele Carella, Marco Gobbi

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

We reviewed the frequency and prognostic significance of FLT3 (fms-like tyrosine kinase receptor-3) and NPM (nucleophosmin) gene mutations and WT1 (Wilms' tumor) and BAALC (brain and acute leukemia, cytoplasmic) gene expression in 100 consecutive patients with intermediate and poor cytogenetic risk de novo acute myeloid leukemia (AML) receiving conventional anthracyclineAraC based therapy. We observed a strict relationship between unfavorable karyotype and BAALC >1000 (p=0.0001). Multivariate analysis of 81 patients with intermediate karyotype revealed that younger age (p=0.00009), NPM gene mutation (p=0.002), and WT1 >75th percentile (>2365) (p=0.003) were independent, positive factors for complete remission (CR). WT1 expression above 2365 was correlated also to longer event-free survival (EFS) and overall survival (OS) in the same subset of patients (p=0.003 and p=0.02, respectively); the same finding occurred in younger patients with AML with intermediate karyotype (p=0.008 and p=0.01, respectively). In patients with intermediate karyotype, FLT3 internal tandem duplication (ITD) negatively affected EFS (EFS at 30 months: 30% vs. 6% in FLT3-ITD negative and FLT3 positive patients, respectively; p=0.01) and OS (OS at 30 months: 38% vs. 20%, p=0.03). The positive prognostic value of high WT1 expression does not have a clear explanation; it may be implicated either with WT1 anti-oncogenic function, or with the stimulating effect of WT1 oncogene on the leukemic cellular cycle, possibly associated with an enhanced response to chemotherapy.

Original languageEnglish
Pages (from-to)1961-1969
Number of pages9
JournalLeukemia and Lymphoma
Volume52
Issue number10
DOIs
Publication statusPublished - Oct 2011

Fingerprint

fms-Like Tyrosine Kinase 3
Acute Myeloid Leukemia
Receptor Protein-Tyrosine Kinases
Karyotype
Disease-Free Survival
Survival
Leukemia
Mutation
Wilms Tumor
Brain
Oncogenes
Cytogenetics
Genes
Multivariate Analysis
Gene Expression
Drug Therapy

Keywords

  • BAALC
  • De novo AML
  • FLT3
  • NPM
  • WT1

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

WT1 overexpression at diagnosis may predict favorable outcome in patients with de novo non-M3 acute myeloid leukemia. / Miglino, Maurizio; Colombo, Nicoletta; Pica, Gianmatteo; Grasso, Raffaella; Clavio, Marino; Bergamaschi, Micaela; Ballerini, Filippo; Ghiso, Anna; Ghiggi, Chiara; Mitscheunig, Laura; Beltrami, Germana; Cagnetta, Antonia; Vignolo, Luana; Lucchetti, Maria Vita; Aquino, Sara; Pierri, Ivana; Sessarego, Mario; Carella, Angelo Michele; Gobbi, Marco.

In: Leukemia and Lymphoma, Vol. 52, No. 10, 10.2011, p. 1961-1969.

Research output: Contribution to journalArticle

Miglino, M, Colombo, N, Pica, G, Grasso, R, Clavio, M, Bergamaschi, M, Ballerini, F, Ghiso, A, Ghiggi, C, Mitscheunig, L, Beltrami, G, Cagnetta, A, Vignolo, L, Lucchetti, MV, Aquino, S, Pierri, I, Sessarego, M, Carella, AM & Gobbi, M 2011, 'WT1 overexpression at diagnosis may predict favorable outcome in patients with de novo non-M3 acute myeloid leukemia', Leukemia and Lymphoma, vol. 52, no. 10, pp. 1961-1969. https://doi.org/10.3109/10428194.2011.585673
Miglino, Maurizio ; Colombo, Nicoletta ; Pica, Gianmatteo ; Grasso, Raffaella ; Clavio, Marino ; Bergamaschi, Micaela ; Ballerini, Filippo ; Ghiso, Anna ; Ghiggi, Chiara ; Mitscheunig, Laura ; Beltrami, Germana ; Cagnetta, Antonia ; Vignolo, Luana ; Lucchetti, Maria Vita ; Aquino, Sara ; Pierri, Ivana ; Sessarego, Mario ; Carella, Angelo Michele ; Gobbi, Marco. / WT1 overexpression at diagnosis may predict favorable outcome in patients with de novo non-M3 acute myeloid leukemia. In: Leukemia and Lymphoma. 2011 ; Vol. 52, No. 10. pp. 1961-1969.
@article{fa0fa8c84d794a80b7aa4e08c5b848ca,
title = "WT1 overexpression at diagnosis may predict favorable outcome in patients with de novo non-M3 acute myeloid leukemia",
abstract = "We reviewed the frequency and prognostic significance of FLT3 (fms-like tyrosine kinase receptor-3) and NPM (nucleophosmin) gene mutations and WT1 (Wilms' tumor) and BAALC (brain and acute leukemia, cytoplasmic) gene expression in 100 consecutive patients with intermediate and poor cytogenetic risk de novo acute myeloid leukemia (AML) receiving conventional anthracyclineAraC based therapy. We observed a strict relationship between unfavorable karyotype and BAALC >1000 (p=0.0001). Multivariate analysis of 81 patients with intermediate karyotype revealed that younger age (p=0.00009), NPM gene mutation (p=0.002), and WT1 >75th percentile (>2365) (p=0.003) were independent, positive factors for complete remission (CR). WT1 expression above 2365 was correlated also to longer event-free survival (EFS) and overall survival (OS) in the same subset of patients (p=0.003 and p=0.02, respectively); the same finding occurred in younger patients with AML with intermediate karyotype (p=0.008 and p=0.01, respectively). In patients with intermediate karyotype, FLT3 internal tandem duplication (ITD) negatively affected EFS (EFS at 30 months: 30{\%} vs. 6{\%} in FLT3-ITD negative and FLT3 positive patients, respectively; p=0.01) and OS (OS at 30 months: 38{\%} vs. 20{\%}, p=0.03). The positive prognostic value of high WT1 expression does not have a clear explanation; it may be implicated either with WT1 anti-oncogenic function, or with the stimulating effect of WT1 oncogene on the leukemic cellular cycle, possibly associated with an enhanced response to chemotherapy.",
keywords = "BAALC, De novo AML, FLT3, NPM, WT1",
author = "Maurizio Miglino and Nicoletta Colombo and Gianmatteo Pica and Raffaella Grasso and Marino Clavio and Micaela Bergamaschi and Filippo Ballerini and Anna Ghiso and Chiara Ghiggi and Laura Mitscheunig and Germana Beltrami and Antonia Cagnetta and Luana Vignolo and Lucchetti, {Maria Vita} and Sara Aquino and Ivana Pierri and Mario Sessarego and Carella, {Angelo Michele} and Marco Gobbi",
year = "2011",
month = "10",
doi = "10.3109/10428194.2011.585673",
language = "English",
volume = "52",
pages = "1961--1969",
journal = "Leukemia and Lymphoma",
issn = "1042-8194",
publisher = "Taylor and Francis Ltd.",
number = "10",

}

TY - JOUR

T1 - WT1 overexpression at diagnosis may predict favorable outcome in patients with de novo non-M3 acute myeloid leukemia

AU - Miglino, Maurizio

AU - Colombo, Nicoletta

AU - Pica, Gianmatteo

AU - Grasso, Raffaella

AU - Clavio, Marino

AU - Bergamaschi, Micaela

AU - Ballerini, Filippo

AU - Ghiso, Anna

AU - Ghiggi, Chiara

AU - Mitscheunig, Laura

AU - Beltrami, Germana

AU - Cagnetta, Antonia

AU - Vignolo, Luana

AU - Lucchetti, Maria Vita

AU - Aquino, Sara

AU - Pierri, Ivana

AU - Sessarego, Mario

AU - Carella, Angelo Michele

AU - Gobbi, Marco

PY - 2011/10

Y1 - 2011/10

N2 - We reviewed the frequency and prognostic significance of FLT3 (fms-like tyrosine kinase receptor-3) and NPM (nucleophosmin) gene mutations and WT1 (Wilms' tumor) and BAALC (brain and acute leukemia, cytoplasmic) gene expression in 100 consecutive patients with intermediate and poor cytogenetic risk de novo acute myeloid leukemia (AML) receiving conventional anthracyclineAraC based therapy. We observed a strict relationship between unfavorable karyotype and BAALC >1000 (p=0.0001). Multivariate analysis of 81 patients with intermediate karyotype revealed that younger age (p=0.00009), NPM gene mutation (p=0.002), and WT1 >75th percentile (>2365) (p=0.003) were independent, positive factors for complete remission (CR). WT1 expression above 2365 was correlated also to longer event-free survival (EFS) and overall survival (OS) in the same subset of patients (p=0.003 and p=0.02, respectively); the same finding occurred in younger patients with AML with intermediate karyotype (p=0.008 and p=0.01, respectively). In patients with intermediate karyotype, FLT3 internal tandem duplication (ITD) negatively affected EFS (EFS at 30 months: 30% vs. 6% in FLT3-ITD negative and FLT3 positive patients, respectively; p=0.01) and OS (OS at 30 months: 38% vs. 20%, p=0.03). The positive prognostic value of high WT1 expression does not have a clear explanation; it may be implicated either with WT1 anti-oncogenic function, or with the stimulating effect of WT1 oncogene on the leukemic cellular cycle, possibly associated with an enhanced response to chemotherapy.

AB - We reviewed the frequency and prognostic significance of FLT3 (fms-like tyrosine kinase receptor-3) and NPM (nucleophosmin) gene mutations and WT1 (Wilms' tumor) and BAALC (brain and acute leukemia, cytoplasmic) gene expression in 100 consecutive patients with intermediate and poor cytogenetic risk de novo acute myeloid leukemia (AML) receiving conventional anthracyclineAraC based therapy. We observed a strict relationship between unfavorable karyotype and BAALC >1000 (p=0.0001). Multivariate analysis of 81 patients with intermediate karyotype revealed that younger age (p=0.00009), NPM gene mutation (p=0.002), and WT1 >75th percentile (>2365) (p=0.003) were independent, positive factors for complete remission (CR). WT1 expression above 2365 was correlated also to longer event-free survival (EFS) and overall survival (OS) in the same subset of patients (p=0.003 and p=0.02, respectively); the same finding occurred in younger patients with AML with intermediate karyotype (p=0.008 and p=0.01, respectively). In patients with intermediate karyotype, FLT3 internal tandem duplication (ITD) negatively affected EFS (EFS at 30 months: 30% vs. 6% in FLT3-ITD negative and FLT3 positive patients, respectively; p=0.01) and OS (OS at 30 months: 38% vs. 20%, p=0.03). The positive prognostic value of high WT1 expression does not have a clear explanation; it may be implicated either with WT1 anti-oncogenic function, or with the stimulating effect of WT1 oncogene on the leukemic cellular cycle, possibly associated with an enhanced response to chemotherapy.

KW - BAALC

KW - De novo AML

KW - FLT3

KW - NPM

KW - WT1

UR - http://www.scopus.com/inward/record.url?scp=80053185143&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053185143&partnerID=8YFLogxK

U2 - 10.3109/10428194.2011.585673

DO - 10.3109/10428194.2011.585673

M3 - Article

C2 - 21942328

AN - SCOPUS:80053185143

VL - 52

SP - 1961

EP - 1969

JO - Leukemia and Lymphoma

JF - Leukemia and Lymphoma

SN - 1042-8194

IS - 10

ER -