FLT3-TKD mutation in childhood acute myeloid leukemia.

Liang, D-C; Shih, L-Y; Hung, I-J; Yang, C-P; Chen, S-H; Jaing, T-H; Liu, H-C; Wang, L-Y; Chang, W-H

Liang, D-C; Shih, L-Y; Hung, I-J; Yang, C-P; Chen, S-H; Jaing, T-H; Liu, H-C; Wang, L-Y; Chang, W-H.

Afiliación

Liang DC; 1Division of Pediatric Hematology-Oncology, Mackay Memorial Hospital, Taipei, Taiwan.

Leukemia ; 17(5): 883-6, 2003 May.

Article en En | MEDLINE | ID: mdl-12750701

RESUMEN

Mutations of receptor tyrosine kinases are implicated in the constitutive activation and development of human hematologic malignancies. An internal tandem duplication (ITD) of the juxtamembrane domain-coding sequence of the FLT3 gene (FLT3-ITD) is found in 20-25% of adult acute myeloid leukemia (AML) and at a lower frequency in childhood AML. FLT3-ITD is associated with leukocytosis and a poor prognosis, especially in patients with normal karyotype. Recently, there have been three reports on point mutations at codon 835 of the FLT3 gene (D835 mutations) in adult AML. These mutations are located in the activation loop of the second tyrosine kinase domain (TKD) of FLT3 (FLT3-TKD). The clinical and prognostic relevance of the TKD mutations is less clear. To the best of our knowledge, there has been no report to describe FLT3-TKD mutations in childhood AML. In this pediatric series, FLT3-TKD mutations occurred in three of 91 patients (3.3%), an incidence significantly lower than that of FLT3-ITD (14 of 91 patients, 15.4%) in the same cohort of patients. None of them had both FLT3-TKD and FLT3-ITD mutations. Sequence analysis showed one each of D835 Y, D835 V, and D835 H. Of the three patients carrying FLT3-TKD, two had AML-M3 with one each of L- and V-type PML-RARalpha, and another one had AML-M2 with AML1-ETO. None of our patients with FLT3-TKD had leukocytosis at diagnosis. At bone marrow relapse, one of the four patients examined acquired FLT3-ITD mutation and none gained FLT3-TKD mutation.

Asunto(s)

Sustitución de Aminoácidos; Leucemia Mieloide Aguda/genética; Leucemia Promielocítica Aguda/genética; Mutación Puntual; Proteínas Tirosina Quinasas/genética; Proteínas Proto-Oncogénicas/genética; Proteínas Tirosina Quinasas Receptoras/genética; Adolescente; Niño; Preescolar; Codón/genética; Subunidad alfa 2 del Factor de Unión al Sitio Principal; Cartilla de ADN; Femenino; Humanos; Masculino; Proteínas de Neoplasias/genética; Proteínas de Fusión Oncogénica/genética; Reacción en Cadena de la Polimerasa; Estructura Terciaria de Proteína; Proteína 1 Compañera de Translocación de RUNX1; Receptores de Superficie Celular/genética; Factor de Células Madre/genética; Factores de Transcripción/genética; Tirosina Quinasa 3 Similar a fms

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Tirosina Quinasas / Leucemia Mieloide Aguda / Leucemia Promielocítica Aguda / Proteínas Proto-Oncogénicas / Mutación Puntual / Proteínas Tirosina Quinasas Receptoras / Sustitución de Aminoácidos Tipo de estudio: Prognostic_studies Límite: Adolescent / Child / Child, preschool / Female / Humans / Male Idioma: En Revista: Leukemia Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2003 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Reino Unido

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