Analyses of cytokine responsive signaling of LPXN and enhanced responses caused by ETV6-LPXN

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461437
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Fujita Health University
• Principal Investigator: ABE Akihiro 藤田保健衛生大学, 医学部, 客員准教授 (00432261)
• Co-Investigator(Kenkyū-buntansha): NOBUHIKO Emi 藤田保健衛生大学, 血液内科, 教授 (30185144)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 染色体転座 / ETV6 / LPXN / G-CSF / CXCL12

Outline of Final Research Achievements

LPXN acts as a signal transducing adaptor protein and plays important roles in cell adhesion and spreading. We discovered a novel fusion gene between ETV6 on 12p13 and LPXN on 11q12.1 in leukemic cells of a patient with relapsed acute myeloid leukemia. ETV6-LPXN did not transform the interleukin-3-dependent 32D myeloid cell line; however, an enhanced proliferative response was observed when these cells were treated with G-CSF without inhibition of granulocytic differentiation. The 32D and human leukemia cell lines each transduced with ETV6-LPXN showed enhanced migration towards the chemokine CXCL12. The immunofluorescence data indicated that ETV6-LPXN oligomerized, because it was detected as discrete spots in the cytoplasm, although LPXN was diffusively distributed throughout the cytoplasm. Our data indicate that ETV6-LPXN is associated with progression of leukemia through modulation of G-CSF and CXCL12/CXCR4, potentially acting within the microenvironment of leukemic cells.

Free Research Field

血液内科学