title: Identification of a molecular signature for leukemic promyelocytes and their normal counterparts: Focus on DNA repair genes.
abstract: Acute promyelocytic leukemia (APL) is a clonal expansion of hematopoietic precursors blocked at the promyelocytic stage. Gene expression profiles of APL cells obtained from 16 patients were compared to eight samples of CD34+-derived normal promyelocytes. Malignant promyelocytes showed widespread changes in transcription in comparison to their normal counterpart and 1020 differentially expressed genes were identified. Discriminating genes include transcriptional regulators (FOS, JUN and HOX genes) and genes involved in cell cycle and DNA repair. The strong upregulation in APL of some transcripts (FLT3, CD33, CD44 and HGF) was also confirmed at protein level. Interestingly, a trend toward a transcriptional repression of genes involved in different DNA repair pathways was found in APL and confirmed by real-time polymerase chain reactor (PCR) in a new set of nine APLs. Our results suggest that both inefficient base excision repair and recombinational repair might play a role in APLs development. To investigate the expression pathways underlying the development of APL occurring as a second malignancy (sAPL), we included in our study eight cases of sAPL. Although both secondary and de novo APL were characterized by a strong homogeneity in expression profiling, we identified a small set of differentially expressed genes that discriminate sAPL from de novo cases.
authors.affiliation: Section of Experimental Carcinogenesis, Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Casorelli
authors.forename: E
authors.initials: E
authors.lastname: Tenedini
authors.forename: E
authors.initials: E
authors.lastname: Tagliafico
authors.forename: M F
authors.initials: MF
authors.lastname: Blasi
authors.forename: A
authors.initials: A
authors.lastname: Giuliani
authors.forename: M
authors.initials: M
authors.lastname: Crescenzi
authors.forename: E
authors.initials: E
authors.lastname: Pelosi
authors.forename: U
authors.initials: U
authors.lastname: Testa
authors.forename: C
authors.initials: C
authors.lastname: Peschle
authors.forename: L
authors.initials: L
authors.lastname: Mele
authors.forename: D
authors.initials: D
authors.lastname: Diverio
authors.forename: M
authors.initials: M
authors.lastname: Breccia
authors.forename: F
authors.initials: F
authors.lastname: Lo-Coco
authors.forename: S
authors.initials: S
authors.lastname: Ferrari
authors.forename: M
authors.initials: M
authors.lastname: Bignami
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic; D042381:Granulocyte Precursor Cells / Q000473:pathology* / Q000502:physiology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D016130:Immunophenotyping; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D063268:Sialic Acid Binding Ig-like Lectin 3; D014158:Transcription, Genetic; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D018960:Hyaluronan Receptors; D063268:Sialic Acid Binding Ig-like Lectin 3; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3