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LPXN , a member of the paxillin superfamily, is fused to RUNX1 in an acute myeloid leukemia patient with a t(11;21)(q12;q22) translocation
Author(s) -
Dai HaiPing,
Xue YongQuan,
Zhou JianWei,
Li AiPing,
Wu YaFang,
Pan JinLan,
Wang Yong,
Zhang Jun
Publication year - 2009
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20704
Subject(s) - runx1 , fusion protein , myeloid leukemia , leukemia , chromosomal translocation , biology , cancer research , fusion gene , myeloid , microbiology and biotechnology , immunology , genetics , stem cell , gene , haematopoiesis , recombinant dna
RUNX1 (previously AML1 ) is involved in multiple recurrent chromosomal rearrangements in hematological malignances. Recently, we identified a novel fusion between RUNX1 and LPXN from an acute myeloid leukemia (AML) patient with t(11;21)(q12;q22). This translocation generated four RUNX1/LPXN and one LPXN/RUNX1 chimeric transcripts. Two representative RUNX1/LPXN fusion proteins, RL and RLs, were both found to localize in the nucleus and could bring the CBFB protein into the nucleus like the wild‐type RUNX1. Both fusion proteins inhibit the ability of RUNX1 to transactivate the CSF1R promoter, probably through competition for its target sequences. Unlike RL and RLs, the LPXN/RUNX1 fusion protein LR was found to localize in the cytoplasm. Thus, we believe it has little impact on the transcriptional activity of RUNX1. We also found that fusion proteins RL, RLs, LR, and wild‐type LPXN could confer NIH3T3 cells with malignant transformation characteristics such as more rapid growth, the ability to form colonies in soft agar, and the ability to form solid tumors in the subcutaneous tissue of the BALB/c nude mice. Taken together, our data indicated that the RUNX1/LPXN and LPXN/RUNX1 fusion proteins may play important roles in leukemogenesis and that deregulation of cell adhesion pathways may be pathogenetically important in AML. Our study also suggests that LPXN may play an important role in carcinogenesis. © 2009 Wiley‐Liss, Inc.