Gene expression profiles of erythroid precursors characterise several mechanisms of the action of hydroxycarbamide in sickle cell anaemia.
Hydroxycarbamide (HC) (or hydroxyurea) has been reported to increase fetal haemoglobin levels and improve clinical symptoms in sickle cell anaemia (SCA) patients. However, the complete pathway by which HC acts remains unclear. To study the mechanisms involved in the action of HC, global gene expression profiles were obtained from the bone marrow cells of a SCA patient before and after HC treatment using serial analysis of gene expression. In the comparison of both profiles, 147 differentially expressed transcripts were identified. The functional classification of these transcripts revealed a group of gene categories associated with transcriptional and translational regulation, e.g. EGR-1, CENTB1, ARHGAP4 and RIN3, suggesting a possible role for these pathways in the improvement of clinical symptoms of SCA patients. The genes involved in these mechanisms may represent potential tools for the identification of new targets for SCA therapy.
Costa
Flávia Chagas
FC
The Haematology and Haemotherapy Centre, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil.
da Cunha
Anderson Ferreira
AF
Fattori
André
A
de Sousa Peres
Tarcísio
T
Costa
Gustavo Gilson Lacerda
GG
Machado
Tiago Ferraz
TF
de Albuquerque
Dulcinéia Martins
DM
Gambero
Sheley
S
Lanaro
Carolina
C
Saad
Sara T Olala
ST
Costa
Fernando Ferreira
FF
D000328:Adult; D000755:Anemia, Sickle Cell / Q000188:drug therapy* / Q000235:genetics*; D000986:Antisickling Agents / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000378:metabolism; D002460:Cell Line; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D005914:Globins / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics; D006454:Hemoglobins / Q000235:genetics; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D007473:Ion Channels / Q000235:genetics; D007962:Leukocytes / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010544:Peroxidases / Q000235:genetics; D054464:Peroxiredoxins; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012156:Reticulocytes / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic
D000986:Antisickling Agents; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D006360:Heat-Shock Proteins; D006454:Hemoglobins; D007473:Ion Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D005914:Globins; D010544:Peroxidases; D054464:Peroxiredoxins; D006918:Hydroxyurea