Premium
Aldehyde dehydrogenase‐1a1 is an oncogene suppressor in B cell populations (639.5)
Author(s) -
Yasmeen Rumana,
Meyers Joseph,
Alvarez Carlos,
Benson Don,
Boyaka Prosper,
Ziouzenkova Ouliana
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.639.5
Subject(s) - cd19 , cancer research , biology , retinoic acid , oncogene , carcinogenesis , aldehyde dehydrogenase , b cell , cell , immune system , immunology , cell culture , cell cycle , antibody , biochemistry , enzyme , gene , genetics
Deregulated B cell differentiation contributes to autoimmune disorders, hematological cancers, and aging. Vitamin A metabolite retinoic acid regulates key immune responses. Here, we explore the role of the retinoic acid‐producing enzyme aldehyde dehydrogenase 1a1 (Aldh1a1) in protection against B cell‐mediated oncogenesis. We showed that Aldh1a1 regulated oncogene suppressors during B cell differentiation sequentially through 1) retinoic acid receptor alpha (Rara) in IgG1+/CD19‐ and 2) zinc finger protein Zfp423 and peroxisome proliferator‐activated receptor gamma (Pparg) in IgG1+/CD19+ splenocytes. Aldh1a1‐deficient mice (Aldh1a1‐/‐ ), displaying pronounced expression of proto‐oncogenic genes c‐Fos, c‐Jun, and Hoxa10 in splenic IgG1+/CD19‐ and IgG1+/CD19+ B cells gave rise to splenomegaly. Human multiple myeloma (MM) B cells did not express Aldh1a1 (n=74 MM vs n=37 healthy patients). Moreover, ectopic Aldh1a1 expression in human MM B cell lines lacking Aldh1a1, rescued Rara and Znf423 expressions in these cells. Our data provide evidence that Aldh1a1 is an oncogene suppressor in specific splenic IgG1+/CD19‐ and IgG1+/CD19+ B cell populations and suggest a mechanism by which this enzyme can potentiate B cell resistance to oncogenesis. Grant Funding Source : Supported by National Center for Advancing Translational Sciences