Hydroxycarbamide modulates components involved in the regulation of adenosine levels in blood cells from sickle-cell anemia patients.
Recent studies have demonstrated the role of adenosine (ADO) in sickle-cell anemia (SCA). ADO is produced by CD39 and CD73 and converted to inosine by adenosine deaminase (ADA). We evaluated the effects of hydroxycarbamide (HU) treatment on the modulation of adenosine levels in SCA patients. The expressions of CD39, CD73, and CD26 were evaluated by flow cytometry on blood cells in 15 HU-treated and 17 untreated patients and 10 healthy individuals. RNA was extracted from monocytes, and ADA gene expression was quantified by real-time PCR. ADA activity was also evaluated. We found that ADA transcripts were two times higher in monocytes of HU-treated patients, compared with untreated (P = 0.039). Monocytes of HU-treated patients expressed CD26, while monocytes of controls and untreated patients did not (P = 0.023). In treated patients, a lower percentage of T lymphocytes expressed CD39 compared with untreated (P = 0.003), and the percentage of T regulatory (Treg) cells was reduced in the treated group compared with untreated (P = 0.017) and controls (P = 0.0009). Besides, HU-treated patients displayed increased ADA activity, compared with untreated. Our results indicate a novel mechanism of action of HU mediated by the reduction of adenosine levels and its effects on pathophysiological processes in SCA.
National Institute of Science and Technology in Stem Cell and Cell Therapy (INCTC), Center for Cell Therapy (CTC) and Regional Blood Center, Faculty of Medicine (FMRP), University of São Paulo (USP), Rua Tenente Catão Roxo, 2.501, Bairro Monte Alegre, Campus Universitário, Ribeirão Preto, São Paulo, 14051-140, Brazil, acristina@hemocentro.fmrp.usp.br.
Ana C
AC
Silva-Pinto
Carolina
C
Dias-Carlos
Felipe
F
Saldanha-Araujo
Flávia I S
FI
Ferreira
Patrícia V B
PV
Palma
Amélia G
AG
Araujo
Regina H C
RH
Queiroz
Jacques
J
Elion
Dimas T
DT
Covas
Marco A
MA
Zago
Rodrigo A
RA
Panepucci
D015720:5'-Nucleotidase / Q000235:genetics / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000986:Antisickling Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001081:Apyrase / Q000235:genetics / Q000378:metabolism; D001773:Blood Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology* / Q000627:therapeutic use; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000235:genetics; D008875:Middle Aged; D055815:Young Adult
D015703:Antigens, CD; D000986:Antisickling Agents; D058851:GPI-Linked Proteins; D015720:5'-Nucleotidase; C548241:NT5E protein, human; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine; D006918:Hydroxyurea