Original scientific paper
Fms-like Tyrosine Kinase (FLT) 3 and FLT3 Internal Tandem Duplication in Different Types of Adult Leukemia: Analysis of 147 Patients
Hong-Ling Peng
; Division of Hematology/Institute of Molecular Hematology, Second Xiang-Ya Hospital, Central South University, Changsa, Hunan, People's Republic of China
Guang-Sen Zhang
; Division of Hematology/Institute of Molecular Hematology, Second Xiang-Ya Hospital, Central South University, Changsa, Hunan, People's Republic of China
Fan-Jie Gong
; Division of Hematology/Institute of Molecular Hematology, Second Xiang-Ya Hospital, Central South University, Changsa, Hunan, People's Republic of China
Jian-Kai Shen
; Division of Hematology/Institute of Molecular Hematology, Second Xiang-Ya Hospital, Central South University, Changsa, Hunan, People's Republic of China
Yang Zhang
; Division of Oncology, Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People's Republic of China
Yun-Xiao Xu
; Division of Hematology/Institute of Molecular Hematology, Second Xiang-Ya Hospital, Central South University, Changsa, Hunan, People's Republic of China
Wen-Li Zheng
; Division of Hematology/Institute of Molecular Hematology, Second Xiang-Ya Hospital, Central South University, Changsa, Hunan, People's Republic of China
Chong-Wen Dai
; Division of Hematology/Institute of Molecular Hematology, Second Xiang-Ya Hospital, Central South University, Changsa, Hunan, People's Republic of China
Min-Fei Pei
; Division of Hematology/Institute of Molecular Hematology, Second Xiang-Ya Hospital, Central South University, Changsa, Hunan, People's Republic of China
Jun-Jie Yang
; Division of Hematology/Institute of Molecular Hematology, Second Xiang-Ya Hospital, Central South University, Changsa, Hunan, People's Republic of China
Abstract
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.
Keywords
Acute myeloid leukemia; Acute lymphoid leukemia; FLT3 receptor; Chronic myeloid leukemia; Internal tandem duplication; prognosis
Hrčak ID:
35102
URI
Publication date:
15.10.2008.
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