全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...

FLT3 Gene Mutation in Childhood Acute Leukemia: A Preliminary Study

DOI: 10.1155/2014/735453

Full-Text   Cite this paper   Add to My Lib

Abstract:

Introduction. FLT3 is a tyrosine kinase receptor involved in the proliferation and differentiation of hematopoietic stem cells. There are two types of common FLT3 gene mutation, internal tandem duplication and the D835 mutation, which are known to be associated with a poor clinical outcome in acute leukemia patients. Methods. This study evaluates the incidence of FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) in 38 pediatric patients diagnosed with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in Hospital Universiti Sains Malaysia. DNA extraction was done from archive bone marrow samples to determine FLT3-ITD mutations using polymerase chain reaction. Results. In this pediatric series, the age ranges were 2–14 years. However, no FLT3-ITD mutations were detected in any of the samples. Conclusion. This preliminary study suggested that the incidence of FLT3 gene mutation most probably was very low in pediatrics patients diagnosed with acute leukemia. A further study with larger number of patient samples is necessary to confirm the findings and to further appreciate the prognostic value of FLT3-ITD mutation among pediatrics patients. 1. Introduction Fms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase expressed by immature hematopoietic cells. FLT3 ligand is expressed by marrow stromal cells and other cells and synergizes with other growth factors to stimulate proliferation and differentiation of stem cells, progenitor cells, dendritic cells, and natural killer cells. In normal hematopoietic cells, FLT3-ITDs (internal tandem duplications) mutations have not been detected in the cord blood and bone marrow [1–5]. In general, there are 2 types of FLT3 mutations which are internal tandem duplications (FLT3/ITD mutations) in or near the juxtamembrane domain of the receptor and point mutations resulting in single amino acid substitutions occurring within the activation loop of the tyrosine kinase domain (FLT3/TKD mutations). Both mutations are known to be associated with a poor clinical outcome in acute leukemia patients. The incidence of FLT3/ITD mutations varies according to age and clinical risk group, being less common in pediatric acute myeloid leukemia (AML) and in AML arising from an antecedent myelodysplastic syndrome. FLT3 mutations are genetic changes that have been reported to have prognostic significance in acute myeloid leukemia (AML) [6]. Study by Thiede et al. in 2002 analyzed the prevalence of FLT3-ITD mutations in 979 AML patients, with 20.4% found to be positive. However, the tandem duplication

References

[1]  A. M. Turner, N. L. Lin, S. Issarachai, S. D. Lyman, and V. C. Broudy, “FLT3 receptor expression on the surface of normal and malignant human hematopoietic cells,” Blood, vol. 88, no. 9, pp. 3383–3390, 1996.
[2]  D. G. Gilliland and J. D. Griffin, “The roles of FLT3 in hematopoiesis and leukemia,” Blood, vol. 100, no. 5, pp. 1532–1542, 2002.
[3]  H. Dehbi, Y. Kassogue, S. Nasserddine, A. Quessar, and S. Nadifi, “FLT3-ITD incidence and FLT-D835 mutations in acute myeloid leukemia patients with normal karyotype in Morocco: a preliminary study,” Middle East Journal of Cancer, vol. 4, no. 1, pp. 1–5, 2013.
[4]  M. Levis, “FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013?” ASH Education Book, vol. 2013, no. 1, pp. 220–226, 2013.
[5]  D. Yassin and I. Sidhom, “Internal tandem duplication of FLT3 gene in egyptian pediatric acute myeloid leukemia and acute lymphoblastic leukemia,” Journal of the Egyptian National Cancer Institute, vol. 15, no. 1, pp. 17–23, 2003.
[6]  S. Bang, Y. A. Jeong, J. Park et al., “Low frequency and variability of FLT3 mutations in Korean patients with acute myeloid leukemia,” Journal of Korean Medical Science, vol. 23, no. 5, pp. 833–837, 2008.
[7]  C. Thiede, C. Steudel, B. Mohr et al., “Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis,” Blood, vol. 99, no. 12, pp. 4326–4335, 2002.
[8]  A. Y. C. Tan, D. A. Westerman, D. A. Carney, J. F. Seymour, S. Juneja, and A. Dobrovic, “Detection of NPM1 exon 12 mutations and FLT3—internal tandem duplications by high resolution melting analysis in normal karyotype acute myeloid leukemia,” Journal of Hematology and Oncology, vol. 1, no. 1, article 10, 2008.
[9]  T. Iwai, S. Yokota, M. Nakao et al., “Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia,” Leukemia, vol. 13, no. 1, pp. 38–43, 1999.
[10]  A. F. A. Nurul, H. Rosline, D. A. Abu et al., “Low incidence of FLT3 gene mutation among Malay patients with Acute Myeloid Leukaemia: a preliminary study,” Asia-Pacific Journal of Molecular Biology and Biotechnology, vol. 19, no. 22, pp. 57–62, 2011.
[11]  S. Scholl, C. Theuer, V. Scheble et al., “Clinical impact of nucleophosmin mutations and Flt3 internal tandem duplications in patients older than 60 yr with acute myeloid leukaemia,” European Journal of Haematology, vol. 80, no. 3, pp. 208–215, 2008.
[12]  M. Nakao, S. Yokota, T. Iwai et al., “Internal tandem duplication of the flt3 gene found in acute myeloid leukemia,” Leukemia, vol. 10, no. 12, pp. 1911–1918, 1996.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133