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

doi:10.3324/haematol.2012.062638

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

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35 Scopus citations

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 language	English (US)
Pages (from-to)	1242-1245
Number of pages	4
Journal	Haematologica
Volume	97
Issue number	8
DOIs	https://doi.org/10.3324/haematol.2012.062638
State	Published - Aug 1 2012
Externally published	Yes

Keywords

Acute myeloid leukemia
FLT3
Internal tandem duplication
Minimal residual disease
Mutations

ASJC Scopus subject areas

Hematology

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10.3324/haematol.2012.062638

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Nazha, A., Cortes, J., Faderl, S., Pierce, S., Daver, N., Kadia, T., Borthakur, G., Luthra, R., Kantarjian, H., & Ravandi, F. (2012). 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. Haematologica, 97(8), 1242-1245. https://doi.org/10.3324/haematol.2012.062638

Nazha, A, Cortes, J, Faderl, S, Pierce, S, Daver, N, Kadia, T, Borthakur, G, Luthra, R, Kantarjian, H & Ravandi, F 2012, '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', Haematologica, vol. 97, no. 8, pp. 1242-1245. https://doi.org/10.3324/haematol.2012.062638

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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.",

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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.

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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

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