Association of Fms-like tyrosine kinase-3 mutation with the occurrence and prognosis of leukemia in patients with leukemia
- VernacularTitle:白血病患者Flt-3基因突变及其与白血病发生、预后的关系
- Author:
Tong WANG
;
Jie WANG
- Publication Type:Journal Article
- From:Chinese Journal of Tissue Engineering Research
2007;11(37):7509-7512
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: Fms-like tyrosine kinase-3 (FLT3) gene is one of the receptors for growth factors in early hematogenesis. By binding to its ligand (FL), FLT3 regulates the proliferation and differentiation of hematopoietic stem/pregenitor cells via cell signal transduction pathway. FLT3 juxtamembrane internal tandem duplication (ITD)mutation is correlated with leukemia onset, development and act as an independent factor for poor prognosis.OBJECTIVE: To explore the relationship between Flt-3/ITD mutation and acute leukemia (AL), and analyze its clinical implication.DESIGN: A repetitive measurement.SETTING: Department of Biochemistry and Molecular Biology, Shenyang Medical College.PARTICIPANTS: Totally 147 samples of leukemia patients were diagnosed by morphological bone marrow biopsy in Shenyang Central Hospitals affiliated to Shenyang Medical College from January 1999 to October 2004. They were 95 males and 52 females with the mean age of 14.5 years old (5-23 years old). According to FAB standard, there were 62 patients with acute leukemia [including 33 cases of acute myelocytic leukemia (AMLs, M1, M2), 3 cases of acute myelo-monocytic leukemia (AMMOLs, M4), 18 cases of acute monocytic leukemia (AMOLs, M5), 8 cases of acute megakaryocytic leukemia (AMKLs, M7)], 43 patients with acute lymphoblastic leukemia (ALLs), 13 patietns with juvenile chronic myelocytic leukemia (JCMLs) and 29 patients with myelodysplastic syndrome (MDSs). Informed contents were obtained from all the participants.METHOD: Flt-3/ITD was detected with polymerase chain reaction (PCR) sequence in the 147 leukemia patients.MArN OUTCOME MEASURES: The clinical manifestations and prognosis were observed in the ALL patients with Flt-3/ITD;The Flt-3 gene expression, Flt-3/ITD positive rate, duplication region and length were detected in all kinds of leukemia.to Flt-3 gene products, including 3 cases of AMLs (M1, M2), 1 case of AMMOL (M4), and 1 case of AMOL (M5). DNA sequencing and blast alignment revealed that ITDs existed in all samples with unusual products within exon 11, in various region and length (33-72 bp). Expression of Flt-3 in different levels was found in 43 cases of ALL, 29 cases of Flt-3/ITD all died short after the diagnosis, and the mean life span of was only 10.8 months.
