Prognostic value of internal tandem duplication of the FLT3 gene in childhood acute myelogenous leukemia

Masaru Kondo, Keizo Horibe, Yoshiyuki Takahashi, Kimikazu Matsumoto, Minoru Fukuda, Jun Inaba, Koji Kato, Seiji Kojima, Takaharu Matsuyama

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Background. Recently, an internal tandem duplication of the FLT3 gene (FLT3/ITD) was found in 20% of adult cases of acute myelogenous leukemia (AML), and this length abnormality was suggested to be associated with leukemic progression. Procedure. We examined the mRNA expression of the FLT3 gene by using reverse transcription-polymerase chain reaction (RT-PCR) in 64 children with AML, and further abnormal transcripts were cloned and sequenced. Results. An unexpected longer product was found in seven patients (11%) by RT-PCR of the FLT3 gene. Sequence analysis of these abnormal products revealed the presence of tandemly duplicated fragments in all seven patients. Three factors were identified to be associated with high incidence of FLT3/ITD; older patients (≥10 years) (P = 0.049), high WBC count (≥50,000/μl) at presentation (P = 0.002), and M3 in FAB subtypes (P = 0.002). Induction failure was observed in 3 (43%) of 7 patients with FLT3/ITD. Only FLT3/ITD was identified as a significant risk factor for induction failure by univariate analysis (P = 0.013), although it was not significant by multivariate analysis (P = 0.11). The Kaplan-Meier estimate of event-free survival rate at 5 years was 14% for patients with FLT3/ITD, which was significantly lower in comparison with 69% for patients without FLT3/ITD (P = 0.003). This finding was also identified by multivariate analysis (P = 0.01). Conclusions. In this study, FLT3/ITD was observed in 11% of childhood AML and identified to be associated with poor prognosis. A large prospective study with uniform treatment is necessary to confirm our results.

Original languageEnglish
Pages (from-to)525-529
Number of pages5
JournalMedical and Pediatric Oncology
Volume33
Issue number6
DOIs
Publication statusPublished - Dec 1 1999
Externally publishedYes

Fingerprint

Gene Duplication
Acute Myeloid Leukemia
Reverse Transcription
Multivariate Analysis
Polymerase Chain Reaction
Kaplan-Meier Estimate
Disease-Free Survival
Sequence Analysis
Survival Rate
Prospective Studies
Gene Expression
Messenger RNA
Incidence
Genes

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Oncology
  • Cancer Research

Cite this

Prognostic value of internal tandem duplication of the FLT3 gene in childhood acute myelogenous leukemia. / Kondo, Masaru; Horibe, Keizo; Takahashi, Yoshiyuki; Matsumoto, Kimikazu; Fukuda, Minoru; Inaba, Jun; Kato, Koji; Kojima, Seiji; Matsuyama, Takaharu.

In: Medical and Pediatric Oncology, Vol. 33, No. 6, 01.12.1999, p. 525-529.

Research output: Contribution to journalArticle

Kondo, Masaru ; Horibe, Keizo ; Takahashi, Yoshiyuki ; Matsumoto, Kimikazu ; Fukuda, Minoru ; Inaba, Jun ; Kato, Koji ; Kojima, Seiji ; Matsuyama, Takaharu. / Prognostic value of internal tandem duplication of the FLT3 gene in childhood acute myelogenous leukemia. In: Medical and Pediatric Oncology. 1999 ; Vol. 33, No. 6. pp. 525-529.
@article{7accb90caae04beb9b17fdd5f8c1700a,
title = "Prognostic value of internal tandem duplication of the FLT3 gene in childhood acute myelogenous leukemia",
abstract = "Background. Recently, an internal tandem duplication of the FLT3 gene (FLT3/ITD) was found in 20{\%} of adult cases of acute myelogenous leukemia (AML), and this length abnormality was suggested to be associated with leukemic progression. Procedure. We examined the mRNA expression of the FLT3 gene by using reverse transcription-polymerase chain reaction (RT-PCR) in 64 children with AML, and further abnormal transcripts were cloned and sequenced. Results. An unexpected longer product was found in seven patients (11{\%}) by RT-PCR of the FLT3 gene. Sequence analysis of these abnormal products revealed the presence of tandemly duplicated fragments in all seven patients. Three factors were identified to be associated with high incidence of FLT3/ITD; older patients (≥10 years) (P = 0.049), high WBC count (≥50,000/μl) at presentation (P = 0.002), and M3 in FAB subtypes (P = 0.002). Induction failure was observed in 3 (43{\%}) of 7 patients with FLT3/ITD. Only FLT3/ITD was identified as a significant risk factor for induction failure by univariate analysis (P = 0.013), although it was not significant by multivariate analysis (P = 0.11). The Kaplan-Meier estimate of event-free survival rate at 5 years was 14{\%} for patients with FLT3/ITD, which was significantly lower in comparison with 69{\%} for patients without FLT3/ITD (P = 0.003). This finding was also identified by multivariate analysis (P = 0.01). Conclusions. In this study, FLT3/ITD was observed in 11{\%} of childhood AML and identified to be associated with poor prognosis. A large prospective study with uniform treatment is necessary to confirm our results.",
author = "Masaru Kondo and Keizo Horibe and Yoshiyuki Takahashi and Kimikazu Matsumoto and Minoru Fukuda and Jun Inaba and Koji Kato and Seiji Kojima and Takaharu Matsuyama",
year = "1999",
month = "12",
day = "1",
doi = "10.1002/(SICI)1096-911X(199912)33:6<525::AID-MPO1>3.0.CO;2-8",
language = "English",
volume = "33",
pages = "525--529",
journal = "Pediatric Blood and Cancer",
issn = "1545-5009",
publisher = "Wiley-Liss Inc.",
number = "6",

}

TY - JOUR

T1 - Prognostic value of internal tandem duplication of the FLT3 gene in childhood acute myelogenous leukemia

AU - Kondo, Masaru

AU - Horibe, Keizo

AU - Takahashi, Yoshiyuki

AU - Matsumoto, Kimikazu

AU - Fukuda, Minoru

AU - Inaba, Jun

AU - Kato, Koji

AU - Kojima, Seiji

AU - Matsuyama, Takaharu

PY - 1999/12/1

Y1 - 1999/12/1

N2 - Background. Recently, an internal tandem duplication of the FLT3 gene (FLT3/ITD) was found in 20% of adult cases of acute myelogenous leukemia (AML), and this length abnormality was suggested to be associated with leukemic progression. Procedure. We examined the mRNA expression of the FLT3 gene by using reverse transcription-polymerase chain reaction (RT-PCR) in 64 children with AML, and further abnormal transcripts were cloned and sequenced. Results. An unexpected longer product was found in seven patients (11%) by RT-PCR of the FLT3 gene. Sequence analysis of these abnormal products revealed the presence of tandemly duplicated fragments in all seven patients. Three factors were identified to be associated with high incidence of FLT3/ITD; older patients (≥10 years) (P = 0.049), high WBC count (≥50,000/μl) at presentation (P = 0.002), and M3 in FAB subtypes (P = 0.002). Induction failure was observed in 3 (43%) of 7 patients with FLT3/ITD. Only FLT3/ITD was identified as a significant risk factor for induction failure by univariate analysis (P = 0.013), although it was not significant by multivariate analysis (P = 0.11). The Kaplan-Meier estimate of event-free survival rate at 5 years was 14% for patients with FLT3/ITD, which was significantly lower in comparison with 69% for patients without FLT3/ITD (P = 0.003). This finding was also identified by multivariate analysis (P = 0.01). Conclusions. In this study, FLT3/ITD was observed in 11% of childhood AML and identified to be associated with poor prognosis. A large prospective study with uniform treatment is necessary to confirm our results.

AB - Background. Recently, an internal tandem duplication of the FLT3 gene (FLT3/ITD) was found in 20% of adult cases of acute myelogenous leukemia (AML), and this length abnormality was suggested to be associated with leukemic progression. Procedure. We examined the mRNA expression of the FLT3 gene by using reverse transcription-polymerase chain reaction (RT-PCR) in 64 children with AML, and further abnormal transcripts were cloned and sequenced. Results. An unexpected longer product was found in seven patients (11%) by RT-PCR of the FLT3 gene. Sequence analysis of these abnormal products revealed the presence of tandemly duplicated fragments in all seven patients. Three factors were identified to be associated with high incidence of FLT3/ITD; older patients (≥10 years) (P = 0.049), high WBC count (≥50,000/μl) at presentation (P = 0.002), and M3 in FAB subtypes (P = 0.002). Induction failure was observed in 3 (43%) of 7 patients with FLT3/ITD. Only FLT3/ITD was identified as a significant risk factor for induction failure by univariate analysis (P = 0.013), although it was not significant by multivariate analysis (P = 0.11). The Kaplan-Meier estimate of event-free survival rate at 5 years was 14% for patients with FLT3/ITD, which was significantly lower in comparison with 69% for patients without FLT3/ITD (P = 0.003). This finding was also identified by multivariate analysis (P = 0.01). Conclusions. In this study, FLT3/ITD was observed in 11% of childhood AML and identified to be associated with poor prognosis. A large prospective study with uniform treatment is necessary to confirm our results.

UR - http://www.scopus.com/inward/record.url?scp=0032757551&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032757551&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1096-911X(199912)33:6<525::AID-MPO1>3.0.CO;2-8

DO - 10.1002/(SICI)1096-911X(199912)33:6<525::AID-MPO1>3.0.CO;2-8

M3 - Article

C2 - 10573574

AN - SCOPUS:0032757551

VL - 33

SP - 525

EP - 529

JO - Pediatric Blood and Cancer

JF - Pediatric Blood and Cancer

SN - 1545-5009

IS - 6

ER -