title: PRAME expression is not associated with down-regulation of retinoic acid signaling in primary acute myeloid leukemia.
abstract: The tumor antigen preferentially expressed antigen of melanoma (PRAME) is frequently overexpressed in a wide variety of malignant diseases, including acute myeloid leukemia (AML). It was recently shown that PRAME can function as a repressor of retinoic acid signaling, as indicated by down-regulation of retinoic acid receptor-beta (RARB) and cyclin-dependent kinase inhibitor 1A (CDKN1A). Another study suggested that PRAME can induce caspase-independent apoptosis via down-regulation of heat shock 27-kDa protein 1 (HSPB1) and S100 calcium-binding protein A4 (S100A4). The transcriptional repression of PRAME depends on the formation of a complex with the enhancer of zeste homolog 2 (EZH2). To test whether these mechanisms play an important roll in AML, we analyzed the expression of PRAME, EZH2, RARB, HSPB1, S100A4, and CDKN1A by real-time polymerase chain reaction in primary leukemic cells from 52 children with AML. All genes were expressed in many patients, but the level of expression of the last four genes was not associated with either PRAME expression or PRAME and EZH2 co-expression. In conclusion, the above mechanisms do not seem to play a major role in the pathogenesis of AML; they could be neutralized by other pathways that affect the same targets.
authors: University Children's Hospital Ulm, Eythstrasse 24, Ulm 89075, Germany. Daniel@Steinba.ch
authors: Daniel
authors: D
authors: Steinbach
authors: Nadine
authors: N
authors: Pfaffendorf
authors: Susan
authors: S
authors: Wittig
authors: Bernd
authors: B
authors: Gruhn
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor; D002648:Child; D002675:Child, Preschool; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D063151:Polycomb Repressive Complex 2; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; C404944:PRAME protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018168:Receptors, Retinoic Acid; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D014157:Transcription Factors; C082925:retinoic acid receptor beta; C077591:S100A4 protein, human; D014212:Tretinoin; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2