Activating internal tandem duplication mutations of the fms-like tyrosine kinase-3 (FLT3-ITD) at complete response and relapse in patients with acute myeloid leukemia

Aziz Nazha, Jorge Cortes, Stefan Faderl, Sherry Pierce, Naval Daver, Tapan Kadia, Gautam Borthakur, Raja Luthra, Hagop Kantarjian, Farhad Ravandi

Research output: Contribution to journalArticle

Abstract

FMS-like tyrosine kinase 3 internal tandem duplication (FLT3- ITD) mutations are among the most frequent molecular aberrations in patients with acute myeloid leukemia. We retrospectively analyzed 324 patients with acute myeloid leukemia treated with front-line induction chemotherapy between October 2004 and March 2010. Fifty-six patients had FLT3-ITD mutation at diagnosis. Fifty-one (91%) patients with FLT3-ITD achieved complete remission. Thirteen patients had FLT3 analysis at complete remission. None had FLT3-ITD. Twenty-five (49%) patients with FLT3-ITD relapsed. Of these, 13 (52%) had FLT3-ITD at relapse (3 negative and 9 not done). Among the 201 patients without FLT3- ITD at diagnosis who achieved complete remission, 77 (38%) relapsed among whom 8 (10%) patients acquired FLT3- ITD clone. We conclude that FLT3-ITD mutations are unstable at follow up and may occur for the first time at relapse. Therefore, FLT3- ITD is not a reliable marker for minimal residual disease in acute myeloid leukemia.

Original languageEnglish (US)
Pages (from-to)1242-1245
Number of pages4
JournalHaematologica
Volume97
Issue number8
DOIs
StatePublished - Aug 1 2012
Externally publishedYes

Fingerprint

fms-Like Tyrosine Kinase 3
Acute Myeloid Leukemia
Recurrence
Mutation
Protein-Tyrosine Kinases
Induction Chemotherapy
Residual Neoplasm
Clone Cells

Keywords

  • Acute myeloid leukemia
  • FLT3
  • Internal tandem duplication
  • Minimal residual disease
  • Mutations

ASJC Scopus subject areas

  • Hematology

Cite this

Activating internal tandem duplication mutations of the fms-like tyrosine kinase-3 (FLT3-ITD) at complete response and relapse in patients with acute myeloid leukemia. / Nazha, Aziz; Cortes, Jorge; Faderl, Stefan; Pierce, Sherry; Daver, Naval; Kadia, Tapan; Borthakur, Gautam; Luthra, Raja; Kantarjian, Hagop; Ravandi, Farhad.

In: Haematologica, Vol. 97, No. 8, 01.08.2012, p. 1242-1245.

Research output: Contribution to journalArticle

Nazha, Aziz ; Cortes, Jorge ; Faderl, Stefan ; Pierce, Sherry ; Daver, Naval ; Kadia, Tapan ; Borthakur, Gautam ; Luthra, Raja ; Kantarjian, Hagop ; Ravandi, Farhad. / Activating internal tandem duplication mutations of the fms-like tyrosine kinase-3 (FLT3-ITD) at complete response and relapse in patients with acute myeloid leukemia. In: Haematologica. 2012 ; Vol. 97, No. 8. pp. 1242-1245.
@article{c4bfd863a3314d0fa5c5bbca41c46c95,
title = "Activating internal tandem duplication mutations of the fms-like tyrosine kinase-3 (FLT3-ITD) at complete response and relapse in patients with acute myeloid leukemia",
abstract = "FMS-like tyrosine kinase 3 internal tandem duplication (FLT3- ITD) mutations are among the most frequent molecular aberrations in patients with acute myeloid leukemia. We retrospectively analyzed 324 patients with acute myeloid leukemia treated with front-line induction chemotherapy between October 2004 and March 2010. Fifty-six patients had FLT3-ITD mutation at diagnosis. Fifty-one (91{\%}) patients with FLT3-ITD achieved complete remission. Thirteen patients had FLT3 analysis at complete remission. None had FLT3-ITD. Twenty-five (49{\%}) patients with FLT3-ITD relapsed. Of these, 13 (52{\%}) had FLT3-ITD at relapse (3 negative and 9 not done). Among the 201 patients without FLT3- ITD at diagnosis who achieved complete remission, 77 (38{\%}) relapsed among whom 8 (10{\%}) patients acquired FLT3- ITD clone. We conclude that FLT3-ITD mutations are unstable at follow up and may occur for the first time at relapse. Therefore, FLT3- ITD is not a reliable marker for minimal residual disease in acute myeloid leukemia.",
keywords = "Acute myeloid leukemia, FLT3, Internal tandem duplication, Minimal residual disease, Mutations",
author = "Aziz Nazha and Jorge Cortes and Stefan Faderl and Sherry Pierce and Naval Daver and Tapan Kadia and Gautam Borthakur and Raja Luthra and Hagop Kantarjian and Farhad Ravandi",
year = "2012",
month = "8",
day = "1",
doi = "10.3324/haematol.2012.062638",
language = "English (US)",
volume = "97",
pages = "1242--1245",
journal = "Haematologica",
issn = "0390-6078",
publisher = "Ferrata Storti Foundation",
number = "8",

}

TY - JOUR

T1 - Activating internal tandem duplication mutations of the fms-like tyrosine kinase-3 (FLT3-ITD) at complete response and relapse in patients with acute myeloid leukemia

AU - Nazha, Aziz

AU - Cortes, Jorge

AU - Faderl, Stefan

AU - Pierce, Sherry

AU - Daver, Naval

AU - Kadia, Tapan

AU - Borthakur, Gautam

AU - Luthra, Raja

AU - Kantarjian, Hagop

AU - Ravandi, Farhad

PY - 2012/8/1

Y1 - 2012/8/1

N2 - FMS-like tyrosine kinase 3 internal tandem duplication (FLT3- ITD) mutations are among the most frequent molecular aberrations in patients with acute myeloid leukemia. We retrospectively analyzed 324 patients with acute myeloid leukemia treated with front-line induction chemotherapy between October 2004 and March 2010. Fifty-six patients had FLT3-ITD mutation at diagnosis. Fifty-one (91%) patients with FLT3-ITD achieved complete remission. Thirteen patients had FLT3 analysis at complete remission. None had FLT3-ITD. Twenty-five (49%) patients with FLT3-ITD relapsed. Of these, 13 (52%) had FLT3-ITD at relapse (3 negative and 9 not done). Among the 201 patients without FLT3- ITD at diagnosis who achieved complete remission, 77 (38%) relapsed among whom 8 (10%) patients acquired FLT3- ITD clone. We conclude that FLT3-ITD mutations are unstable at follow up and may occur for the first time at relapse. Therefore, FLT3- ITD is not a reliable marker for minimal residual disease in acute myeloid leukemia.

AB - FMS-like tyrosine kinase 3 internal tandem duplication (FLT3- ITD) mutations are among the most frequent molecular aberrations in patients with acute myeloid leukemia. We retrospectively analyzed 324 patients with acute myeloid leukemia treated with front-line induction chemotherapy between October 2004 and March 2010. Fifty-six patients had FLT3-ITD mutation at diagnosis. Fifty-one (91%) patients with FLT3-ITD achieved complete remission. Thirteen patients had FLT3 analysis at complete remission. None had FLT3-ITD. Twenty-five (49%) patients with FLT3-ITD relapsed. Of these, 13 (52%) had FLT3-ITD at relapse (3 negative and 9 not done). Among the 201 patients without FLT3- ITD at diagnosis who achieved complete remission, 77 (38%) relapsed among whom 8 (10%) patients acquired FLT3- ITD clone. We conclude that FLT3-ITD mutations are unstable at follow up and may occur for the first time at relapse. Therefore, FLT3- ITD is not a reliable marker for minimal residual disease in acute myeloid leukemia.

KW - Acute myeloid leukemia

KW - FLT3

KW - Internal tandem duplication

KW - Minimal residual disease

KW - Mutations

UR - http://www.scopus.com/inward/record.url?scp=84864739408&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864739408&partnerID=8YFLogxK

U2 - 10.3324/haematol.2012.062638

DO - 10.3324/haematol.2012.062638

M3 - Article

C2 - 22532519

AN - SCOPUS:84864739408

VL - 97

SP - 1242

EP - 1245

JO - Haematologica

JF - Haematologica

SN - 0390-6078

IS - 8

ER -