Dual retrovirus integration tagging: identification of new signaling molecules Fiz1 and Hipk2 that are involved in the IL-7 signaling pathway in B lymphoblastic lymphomas.

Abstract:

:IL-7R, FLT3, and CD43 are surface antigens expressed during the transition from pro-B to pre-B cells in BM. To understand interactions between their signaling pathways, we analyzed spontaneous mouse B-LBLs with dual MLV integration into Stat5a and Fiz1 or Stat5a and Hipk2. MLV integration resulted in up-regulation of these genes in lymphoma cells compared with normal pro-B cells from the BM. In lymphomas with both integrations into Stat5a and Fiz1, increases in phosphorylated STAT5A and expression of c-Myc, a target gene of STAT5A, were observed following stimulation of the FLT3. Clones with the dual integrations grew faster in IL-7 and FLT3L-supplemented medium than clones with Stat5a integration alone. On the other hand, in lymphomas with integrations into Stat5a and Hipk2, increases in phosphorylated STAT5A and expression of c-Myc were observed following cross-linking of CD43. In conclusion, FLT3 and CD43 signaling pathways involve STAT5A via Fiz1 and Hipk2 in B-LBLs. Identification of the dual MLV integration sites in B-LBLs, therefore, will provide an excellent tool for identification of the signaling pathways in B-LBLs.

journal_name

J Leukoc Biol

authors

Tsuruyama T,Imai Y,Takeuchi H,Hiratsuka T,Maruyama Y,Kanaya K,Kaszynski R,Jin G,Okuno T,Ozeki M,Nakamura T,Takakuwa T,Manabe T,Tamaki K,Hiai H

doi

10.1189/jlb.1109748

subject

Has Abstract

pub_date

2010-07-01 00:00:00

pages

107-16

issue

1

eissn

0741-5400

issn

1938-3673

pii

jlb.1109748

journal_volume

88

pub_type

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