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- Soheil Meshinchi
- Clinical Research Division, Fred Hutchinson Cancer Research Center, and
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- Derek L. Stirewalt
- Clinical Research Division, Fred Hutchinson Cancer Research Center, and
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- Todd A. Alonzo
- Children's Oncology Group, Arcadia, CA;
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- Titus J. Boggon
- Department of Pharmacology, Yale University School of Medicine, New Haven, CT; and
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- Robert B. Gerbing
- Children's Oncology Group, Arcadia, CA;
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- Jennifer L. Rocnik
- Division of Hematology/Oncology, Department of Pathology, Brigham and Women's Hospital; the Howard Hughes Medical Institute, Harvard Medical School, Boston, MA
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- Beverly J. Lange
- Children's Oncology Group, Arcadia, CA;
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- D. Gary Gilliland
- Division of Hematology/Oncology, Department of Pathology, Brigham and Women's Hospital; the Howard Hughes Medical Institute, Harvard Medical School, Boston, MA
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- Jerald P. Radich
- Clinical Research Division, Fred Hutchinson Cancer Research Center, and
書誌事項
- 公開日
- 2008-05-15
- DOI
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- 10.1182/blood-2008-01-117770
- 公開者
- American Society of Hematology
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>FLT3 internal tandem duplication (FLT3/ITD) is a common somatic mutation in acute myeloid leukemia (AML) with significant variation in the position, length, and number of duplications of the FLT3 gene. We evaluated these physical characteristics in FLT3/ITD-positive patients who were treated on CCG-2941/2961 and correlated them with clinical outcome. Fiftynine of 77 FLT3/ITD-positive patients (77%) had a single ITD, 16 (21%) had 2 ITDs, and 2 (3%) had 3 ITDs. The length of the duplicated region varied from 6 to 51 amino acids, and in all cases amino acid residues Y591–Y597 were duplicated. Structural analysis demonstrated that Y591–Y597 encodes the switch and zipper regions of the juxtamembrane domain of FLT3. In addition, 24 of 77 patients (31%) had duplication of the critical STAT5 docking sites Y589/591. Patients with longer ITDs had a worse relapse-free survival (19% vs 51%, P = .035), while the presence of more than 1 ITD was not clinically significant. Physical characteristics including the length of FLT3/ITD may influence FLT3 activation state by altering its structure and may impact response to therapy.</jats:p>
収録刊行物
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- Blood
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Blood 111 (10), 4930-4933, 2008-05-15
American Society of Hematology
