The AML1/ETO target gene LAT2 interferes with differentiation of normal hematopoietic precursor cells.
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.
Department of Hematology and Oncology, University of Freiburg, Medical Center, Freiburg, Germany. Electronic address: aitomi.essig@charite.de.
Aitomi
A
Essig
Department of Hematology and Oncology, University of Freiburg, Medical Center, Freiburg, Germany.
Jesus
J
Duque-Afonso
Department of Hematology and Oncology, University of Freiburg, Medical Center, Freiburg, Germany.
Sven
S
Schwemmers
Department of Hematology and Oncology, University of Freiburg, Medical Center, Freiburg, Germany.
Heike L
HL
Pahl
Department of Hematology and Oncology, University of Freiburg, Medical Center, Freiburg, Germany.
Michael
M
Lübbert
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D018952:Antigens, CD34 / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000276:immunology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D000075142:RUNX1 Translocation Partner 1 Protein; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D018952:Antigens, CD34; D050676:Core Binding Factor Alpha 2 Subunit; D007377:Interleukin-3; C419196:LAT2 protein, human; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000075142:RUNX1 Translocation Partner 1 Protein; C493728:RUNX1 protein, human; C082222:RUNX1T1 protein, human; D019089:Stem Cell Factor; D014157:Transcription Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
Acute myeloid leukemia; Adaptor molecule; Erythroid differentiation; Myeloid differentiation