Open AccessAdult T‐cell leukemia cells are characterized by abnormalities of Helios expression that promote T cell growth
Author(s) -
Asanuma Satomi,
Yamagishi Makoto,
Kawanami Katsuaki,
Nakano Kazumi,
SatoOtsubo Aiko,
Muto Satsuki,
Sanada Masashi,
Yamochi Tadanori,
Kobayashi Seiichiro,
Utsunomiya Atae,
Iwanaga Masako,
Yamaguchi Kazunari,
Uchimaru Kaoru,
Ogawa Seishi,
Watanabe Toshiki
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12181
Subject(s) - gene knockdown , t cell leukemia , biology , ectopic expression , phenotype , gene isoform , cell growth , alternative splicing , jurkat cells , leukemia , haematopoiesis , regulator , cancer research , t cell , cell culture , microbiology and biotechnology , gene , genetics , stem cell , immune system
Molecular abnormalities involved in the multistep leukemogenesis of adult T‐cell leukemia ( ATL ) remain to be clarified. Based on our integrated database, we focused on the expression patterns and levels of Ikaros family genes, Ikaros , Helios , and Aiolos , in ATL patients and HTLV ‐1 carriers. The results revealed profound deregulation of Helios expression, a pivotal regulator in the control of T‐cell differentiation and activation. The majority of ATL samples (32/37 cases) showed abnormal splicing of Helios expression, and four cases did not express Helios. In addition, novel genomic loss in Helios locus was observed in 17/168 cases. We identified four ATL ‐specific short Helios isoforms and revealed their dominant‐negative function. Ectopic expression of ATL ‐type Helios isoform as well as knockdown of normal Helios or Ikaros promoted T‐cell growth. Global mRNA profiling and pathway analysis showed activation of several signaling pathways important for lymphocyte proliferation and survival. These data provide new insights into the molecular involvement of Helios function in the leukemogenesis and phenotype of ATL cells, indicating that Helios deregulation is one of the novel molecular hallmarks of ATL .