Fms-like Tyrosine Kinase (FLT) 3 and FLT3 Internal Tandem Duplication in Different Types of Adult Leukemia: Analysis of 147 Patients

Autor: Min-fei Pei, Yunxiao Xu, Jian-kai Shen, Wenli Zheng, Chong-Wen Dai, Yang Zhang, Guangsen Zhang, Fan-Jie Gong, Jun-jie Yang, Hongling Peng
Jazyk: angličtina
Rok vydání: 2008
Předmět:
FLT3 Internal Tandem Duplication
Adult
Male
Leukemia
T-Cell
Adolescent
Acute myeloid leukemia
Acute lymphoid leukemia
FLT3 receptor
Chronic myeloid leukemia
Internal tandem duplication
prognosis
Bone Marrow Cells
Biology
Gene Expression Regulation
Enzymologic
Young Adult
fluids and secretions
Predictive Value of Tests
White blood cell
Leukemia
Myelogenous
Chronic
BCR-ABL Positive
hemic and lymphatic diseases
medicine
Biomarkers
Tumor
Leukemia
B-Cell
Humans
RNA
Messenger
Aged
Acute leukemia
Leukemia
Vascular Endothelial Growth Factor Receptor-1
Reverse Transcriptase Polymerase Chain Reaction
Incidence
Myeloid leukemia
hemic and immune systems
General Medicine
Middle Aged
Clinical Science
medicine.disease
Flow Cytometry
Prognosis
Gene Expression Regulation
Neoplastic
medicine.anatomical_structure
Tandem Repeat Sequences
Mutation
embryonic structures
Cancer research
Female
Bone marrow
Lymphoid leukemia
Chronic myelogenous leukemia
Zdroj: Croatian Medical Journal
Volume 49
Issue 5
ISSN: 1332-8166
0353-9504
Popis: Aim To assess the expression level of fms-like tyrosine kinase 3 (FLT3), the incidence of FLT3/internal tandem duplications (ITD) mutation, and prognostic value of FLT3 changes in different types of adult leukemia. Methods Bone marrow mononuclear cells were isolated from 147 adult patients with leukemia. Reverse transcriptase polymerase chain reaction (PCR) was used to screen FLT3/ITD mutation and quantitative PCR was performed to evaluate the expression of the FLT3 transcript. Flow cytometry was used for detection of FLT3 receptor protein expression on bone marrow mononuclear cells. Pearson correlation analysis was performed to estimate the significance of FLT3. Results FLT3 expression was higher in acute myeloid leukemia and Bacute lymphoid leukemia than in T-acute lymphoid leukemia (P = 0.006, P = 0.001) and chronic myelogenous leukemia (P < 0.001). In chronic myelogenous leukemia, FLT3 expression in blast transformation phase was higher than in acceleration phase (P = 0.023). Surface expression of FLT3 protein was correlated with high percentage of bone marrow blasts and with FLT3 mRNA expression (r = 0.366, P < 0.001) in acute leukemia. FLT3/ITDs in the juxtamembrane domain were found in 25% of patients with acute myeloid leukemia and 7% of patients with acute lymphoid leukemia. FLT3/ITD positive sequences had 36, 42, and 57 nucleotides. FLT3/ITD mutation was associated with a higher white blood cell count, higher marrow blast percentage, and elevated serum lactate dehydrogenase (P = 0.045, P = 0.014, P < 0.001, respectively) and not associated with a higher FLT3 mRNA and FLT3 protein expression, and lower complete remission (P = 0.091, P = 0.060, P = 0.270, respectively). Conclusion FLT3 expression levels differed in different types of adult leukemia. Overexpression of FLT3 and presence of a positive FLT3/ ITD mutation in acute leukemia were associated with unfavorable clinical characteristics and poor prognosis.
Databáze: OpenAIRE
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