Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia

Author:

Stirewalt Derek L.1,Kopecky Kenneth J.1,Meshinchi Soheil1,Engel Julia H.1,Pogosova-Agadjanyan Era L.1,Linsley Jeremy1,Slovak Marilyn L.1,Willman Cheryl L.1,Radich Jerald P.1

Affiliation:

1. From the Clinical Research Division and the Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; the Division of Oncology, University of Washington, Seattle; the Children's Oncology Group, Myeloid Disease Committee, Arcadia, CA; the Department of Cytogenetics, City of Hope National Medical Center, Duarte, CA; and the Department of Pathology and Cell Biology, University of New Mexico School of Medicine, Albuquerque.

Abstract

FLT3 internal tandem duplications (FLT3/ITDs) in the juxtamembrane domain are found in approximately 25% of acute myeloid leukemia (AML) patients, ranging in size from 3 to hundreds of nucleotides. We examined whether the sizes of FLT3/ITDs were associated with clinical outcomes in 151 AML patients enrolled in Southwest Oncology Group studies: S9333 and S9500. FLT3/ITDs were identified in 32% of patients (median ITD size = 39 nucleotides; range, 15-153 nucleotides). The CR rates were 35%, 67%, and 52% for patients with large (≥ 40), small (< 40), and no ITDs, respectively (P = .19). Increasing ITD size was associated with decreasing OS (estimated 5-year OS: large = 13%, small = 26%, and no ITD = 21%, P = .072) and RFS (estimated 5-year RFS: large = 13%, small = 27%, and no ITD = 34%, P = .017). These studies suggest that ITD size may have prognostic significance.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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