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.

• Authors: Aziz Nazha, Jorge Cortes, Stefan Faderl, Sherry Pierce, Naval Daver, Tapan Kadia, Gautam Borthakur, Raja Luthra, Hagop Kantarjian, Farhad Ravandi
• Journal: Haematologica (Haematologica) Vol. 97 Issue 8 Pg. 1242-5 (Aug 2012) ISSN: 1592-8721 [Electronic] Italy
• PMID: 22532519 (Publication Type: Journal Article)

Chemical References

• fms-Like Tyrosine Kinase 3

Topics

• Adolescent
• Adult
• Aged
• Humans
• Karyotype
• Leukemia, Myeloid, Acute (drug therapy, genetics)
• Middle Aged
• Mutation
• Neoplasm, Residual (diagnosis, genetics)
• Prognosis
• Recurrence
• Remission Induction
• Retrospective Studies
• Tandem Repeat Sequences
• Young Adult
• fms-Like Tyrosine Kinase 3 (genetics)