The AML1/ETO target gene LAT2 interferes with differentiation of normal hematopoietic precursor cells

• Published in: Leukemia research 2014-03, Vol.38 (3), p.340-345
• Main Authors: Essig, Aitomi, Duque-Afonso, Jesus, Schwemmers, Sven, Pahl, Heike L, Lübbert, Michael
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; Adaptor molecule; Adaptor Proteins, Signal Transducing - antagonists & inhibitors; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - immunology; Antigens, CD34 - genetics; Antigens, CD34 - immunology; Cell Differentiation - drug effects; Cells, Cultured; Core Binding Factor Alpha 2 Subunit - genetics; Core Binding Factor Alpha 2 Subunit - immunology; Erythroid differentiation; Gene Expression Regulation; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Granulocytes - cytology; Granulocytes - drug effects; Granulocytes - immunology; Hematology, Oncology and Palliative Medicine; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - immunology; Humans; Interleukin-3 - pharmacology; Leukocytes, Mononuclear; Lymphocyte Activation; Lymphocytes - cytology; Lymphocytes - drug effects; Lymphocytes - immunology; Monocytes - cytology; Monocytes - drug effects; Monocytes - immunology; Myeloid differentiation; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - immunology; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; RUNX1 Translocation Partner 1 Protein; Signal Transduction; Stem Cell Factor - pharmacology; Transcription Factors - genetics; Transcription Factors - immunology
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2013.12.014

Abstract The adaptor protein linker activator of T-cells 2 (LAT2) is a known AML1/ETO target gene whose function during normal hematopoiesis is unknown. We addressed the role of LAT2 during erythroid and myeloid differentiation of normal human CD34+ hematopoietic cells. LAT2 is expressed at low levels in CD34+ cells and upregulated during cytokine-induced myeloid and erythroid differentiation. Forced LAT2 expression leads to a delay of erythroid and myeloid differentiation keeping CD34+ cells in a more immature state, whereas LAT2 knockdown accelerates differentiation. It is tempting to speculate that by affecting the differentiation capacity of normal hematopoietic progenitors, LAT2 may contribute to the pathogenesis of AML.