Fms-like tyrosine kinase 3 ligand stimulation induces MLL-rearranged leukemia cells into quiescence resistant to antileukemic agents.

Fms-like tyrosine kinase 3 ligand stimulation induces MLL-rearranged leukemia cells into quiescence resistant to antileukemic agents. Research Abstract Details 

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Fms-like tyrosine kinase 3 ligand stimulation induces MLL-rearranged leukemia cells into quiescence resistant to antileukemic agents. Abstract Text:

Yoshiyuki Furuichi,Kumiko Goi,Takeshi Inukai,Hiroki Sato,Atsushi Nemoto,Kazuya Takahashi,Koshi Akahane,Kinuko Hirose,Hiroko Honna,Itaru Kuroda,Xiaochun Zhang,Keiko Kagami,Yasuhide Hayashi,Kenichi Harigaya,Shinpei Nakazawa,Kanji Sugita,Yoshiyuki Furuichi,Kumiko Goi,Takeshi Inukai,Hiroki Sato,Atsushi Nemoto,Kazuya Takahashi,Koshi Akahane,Kinuko Hirose,Hiroko Honna,Itaru Kuroda,Xiaochun Zhang,Keiko Kagami,Yasuhide Hayashi,Kenichi Harigaya,Shinpei Nakazawa,Kanji Sugita,

Fms-like tyrosine kinase 3 (FLT3) is highly expressed in acute lymphoblastic leukemia with the mixed-lineage leukemia (MLL) gene rearrangement refractory to chemotherapy. We examined the biological effect of FLT3-ligand (FL) on 18 B-precursor leukemic cell lines with variable karyotypic abnormalities, and found that nine of nine MLL-rearranged cell lines with wild-type FLT3, in contrast to other leukemic cell lines, are significantly inhibited in their proliferation in a dose-dependent manner by FL. This inhibition was due to induction of the G0-G1 arrest. A marked up-regulation of p27 by suppression of its protein degradation and an abrogation of constitutive signal transducers and activators of transcription 5 phosphorylation were revealed in arrested leukemia cells after FL stimulation. Importantly, FL treatment rendered not only cell lines but also primary leukemia cells with MLL rearrangement resistant to chemotherapeutic agents. MLL-rearranged leukemia cells adhering to the bone marrow stromal cell line, which expresses FL as the membrane-bound form, were induced to quiescent state resistant to chemotherapeutic agents, but their chemosensitivity was significantly restored in the presence of neutralizing anti-FL antibody. The FL/FLT3 interaction between leukemia cells and bone marrow stromal cells expressing FL at high levels should contribute, at least in part, to persistent minimal-residual disease of MLL-rearranged leukemia in bone marrow.

Fms-like tyrosine kinase 3 ligand stimulation induces MLL-rearranged leukemia cells into quiescence resistant to antileukemic agents. Publishing Authors By Initials

Y Furuichi,K Goi,T Inukai,H Sato,A Nemoto,K Takahashi,K Akahane,K Hirose,H Honna,I Kuroda,X Zhang,K Kagami,Y Hayashi,K Harigaya,S Nakazawa,K Sugita,Y Furuichi,K Goi,T Inukai,H Sato,A Nemoto,K Takahashi,K Akahane,K Hirose,H Honna,I Kuroda,X Zhang,K Kagami,Y Hayashi,K Harigaya,S Nakazawa,K Sugita,

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Fms-like tyrosine kinase 3 ligand stimulation induces MLL-rearranged leukemia cells into quiescence resistant to antileukemic agents. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cancer research

VOLUME: 67

Page Numbers: 9852-61

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 15

MONTH: Oct

YEAR: 2007

Fms-like tyrosine kinase 3 ligand stimulation induces MLL-rearranged leukemia cells into quiescence resistant to antileukemic agents. Information

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LANGUAGE: eng

NlmUniqueID: 2984705

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Grant and Affiliation Information for Fms-like tyrosine kinase 3 ligand stimulation induces MLL-rearranged leukemia cells into quiescence resistant to antileukemic agents.

AFFILIATION: Department of Pediatrics, School of Medicine, University of Yamanashi, Yamanashi, Japan.

Country: United States

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MEDLINETA: Cancer Res

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