Stability and prognostic influence of FLT3 mutations in paired initial and relapsed AML samples

Leukemia
Jacqueline CloosGertjan J L Kaspers

Abstract

In acute myeloid leukemia (AML), activating mutations in the fms-like tyrosine kinase 3 (FLT3) gene predict poor prognosis. We determined FLT3 internal tandem duplications (FLT3/ITD) and D835 point mutations in paired initial and relapse samples from 80 pediatric and adult AML patients. One D835 point mutation was found in an initial pediatric AML sample. Fms-like tyrosine kinase 3/ITDs were present in 21 initial and 22 relapse samples (26.3 and 27.5%, respectively). Interestingly, FLT3/ITD positivity was related to a significantly shorter time to relapse, most pronounced when the ITD-positive status was found at relapse (P<0.001). However, FLT3/ITD status changed between diagnosis and relapse in 14 cases. In four patients, the FLT3/ITD became undetectable at relapse in five patients FLT3/ITDs were only detected at relapse, and in five patients the length or number of FLT3/ITDs changed. Gain of FLT3/ITDs may suggest oligoclonality with selective outgrowth of the FLT3/ITD-positive clone, whereas losses may reflect ITDs in the more mature leukemic cells rather than in the leukemic stem cell, or, alternatively, that other genetic aberrations provided a greater selective advantage. Studying FLT3/ITD kinetics in minimal residual dis...Continue Reading

References

Aug 15, 2002·Blood·D Gary Gilliland, James D Griffin
Jul 12, 2003·Leukemia & Lymphoma·Panagiotis D KottaridisDavid C Linch

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Citations

Jan 30, 2013·International Journal of Hematology·Tomoki Naoe, Hitoshi Kiyoi
Apr 14, 2009·Bone Marrow Transplantation·U BacherT Haferlach
Jun 12, 2012·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Mikako WarrenZhuang Zuo
Jun 27, 2013·Nature Reviews. Clinical Oncology·Christopher S Hourigan, Judith E Karp
Sep 8, 2011·Current Opinion in Hematology·Betul Oran, Marcos de Lima
Feb 9, 2012·Current Opinion in Hematology·Courtney D DiNardo, Selina M Luger
Feb 6, 2013·Current Opinion in Hematology·Elaine Coustan-Smith, Dario Campana
Aug 31, 2012·Science Translational Medicine·Max JanRavindra Majeti
May 1, 2007·Current Hematologic Malignancy Reports·Anna van RhenenGerrit Jan Schuurhuis
Oct 15, 2014·Seminars in Hematology·John S Welch
Feb 22, 2012·Oncogene·M Jan, R Majeti
Nov 19, 2010·Expert Review of Hematology·Gerrit Jan Schuurhuis, Gert Ossenkoppele
Mar 1, 2012·Expert Review of Anticancer Therapy·Gertjan J L Kaspers
Sep 15, 2010·Best Practice & Research. Clinical Haematology·William ArceseUNKNOWN Rome Transplant Network
Dec 5, 2009·Best Practice & Research. Clinical Haematology·Richard M Stone
Mar 27, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Monique TerwijnGerrit Jan Schuurhuis
Jan 24, 2009·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·S Haihua Chu, Donald Small
Aug 12, 2008·Seminars in Oncology·Sylvie D FreemanDavid Grimwade
Mar 18, 2008·Best Practice & Research. Clinical Haematology·Winnie F Tam, D Gary Gilliland
Sep 8, 2015·Bioorganic & Medicinal Chemistry Letters·Xing-Dong LinSheng-Yong Yang
Apr 3, 2008·Hematological Oncology·Tiziana GrafoneGiovanni Martinelli

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