Literature DB >> 18925699

Fms-like tyrosine kinase (FLT) 3 and FLT3 internal tandem duplication in different types of adult leukemia: analysis of 147 patients.

Hong-Ling Peng1, Guang-Sen Zhang, Fan-Jie Gong, Jian-Kai Shen, Yang Zhang, Yun-Xiao Xu, Wen-Li Zheng, Chong-Wen Dai, Min-Fei Pei, Jun-Jie Yang.   

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 B-acute 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.

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Year:  2008        PMID: 18925699      PMCID: PMC2582358          DOI: 10.3325/cmj.2008.5.650

Source DB:  PubMed          Journal:  Croat Med J        ISSN: 0353-9504            Impact factor:   1.351


  30 in total

1.  Constitutive activation of FLT3 stimulates multiple intracellular signal transducers and results in transformation.

Authors:  K F Tse; G Mukherjee; D Small
Journal:  Leukemia       Date:  2000-10       Impact factor: 11.528

2.  FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high-risk group.

Authors:  F M Abu-Duhier; A C Goodeve; G A Wilson; M A Gari; I R Peake; D C Rees; E A Vandenberghe; P R Winship; J T Reilly
Journal:  Br J Haematol       Date:  2000-10       Impact factor: 6.998

3.  Myelodysplastic syndrome with transformation to acute monocytic leukemia with FLT3-ITD mutation following orthotopic liver transplantation.

Authors:  Guang-Sen Zhang; Chong-Wen Dai; Hong-Lin Peng; Yun-Xiao Xu; Min-Fei Pei
Journal:  Leuk Res       Date:  2006-01-18       Impact factor: 3.156

4.  Activating FLT3 mutations are detectable in chronic and blast phase of chronic myeloproliferative disorders other than chronic myeloid leukemia.

Authors:  Pei Lin; Dan Jones; L Jeffrey Medeiros; Weina Chen; Francisco Vega-Vazquez; Rajyalakshmi Luthra
Journal:  Am J Clin Pathol       Date:  2006-10       Impact factor: 2.493

5.  A FLT3 tyrosine kinase inhibitor is selectively cytotoxic to acute myeloid leukemia blasts harboring FLT3 internal tandem duplication mutations.

Authors:  M Levis; K F Tse; B D Smith; E Garrett; D Small
Journal:  Blood       Date:  2001-08-01       Impact factor: 22.113

6.  Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies.

Authors:  Y Yamamoto; H Kiyoi; Y Nakano; R Suzuki; Y Kodera; S Miyawaki; N Asou; K Kuriyama; F Yagasaki; C Shimazaki; H Akiyama; K Saito; M Nishimura; T Motoji; K Shinagawa; A Takeshita; H Saito; R Ueda; R Ohno; T Naoe
Journal:  Blood       Date:  2001-04-15       Impact factor: 22.113

7.  The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials.

Authors:  P D Kottaridis; R E Gale; M E Frew; G Harrison; S E Langabeer; A A Belton; H Walker; K Wheatley; D T Bowen; A K Burnett; A H Goldstone; D C Linch
Journal:  Blood       Date:  2001-09-15       Impact factor: 22.113

8.  Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines.

Authors:  F Hayakawa; M Towatari; H Kiyoi; M Tanimoto; T Kitamura; H Saito; T Naoe
Journal:  Oncogene       Date:  2000-02-03       Impact factor: 9.867

9.  Biological characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplications in the Flt3 gene.

Authors:  W J Rombouts; I Blokland; B Löwenberg; R E Ploemacher
Journal:  Leukemia       Date:  2000-04       Impact factor: 11.528

10.  Mechanism of constitutive activation of FLT3 with internal tandem duplication in the juxtamembrane domain.

Authors:  Hitoshi Kiyoi; Ryuzo Ohno; Ryuzo Ueda; Hidehiko Saito; Tomoki Naoe
Journal:  Oncogene       Date:  2002-04-11       Impact factor: 9.867

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  3 in total

1.  FLT3-ITD with DNMT3A R882 double mutation is a poor prognostic factor in Chinese patients with acute myeloid leukemia after chemotherapy or allogeneic hematopoietic stem cell transplantation.

Authors:  Shanhao Tang; Hongjie Shen; Xinliang Mao; Haiping Dai; Xiaming Zhu; Shengli Xue; Zixuan Ding; Jing Lu; Depei Wu; Xiaowen Tang
Journal:  Int J Hematol       Date:  2017-06-14       Impact factor: 2.490

2.  High FLT3 expression and IL10 (G1082A) polymorphism in poor overall survival in calla acute lymphoblastic leukemia.

Authors:  Dayse Maria Vasconcelos de Deus; Paulo Roberto Eleutério de Souza; Maria Tereza Cartaxo Muniz
Journal:  Mol Biol Rep       Date:  2012-10-20       Impact factor: 2.316

3.  Examination of the FLT3 and NPM1 mutational status in patients with acute myeloid leukemia from southeastern Poland.

Authors:  Dorota Koczkodaj; Szymon Zmorzyński; Małgorzata Michalak-Wojnowska; Ewa Wąsik-Szczepanek; Agata A Filip
Journal:  Arch Med Sci       Date:  2016-02-02       Impact factor: 3.318

  3 in total

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