RGD Reference Report - Hydroxycarbamide alters erythroid gene expression in children with sickle cell anaemia. - Rat Genome Database

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Hydroxycarbamide alters erythroid gene expression in children with sickle cell anaemia.

Authors: Flanagan, JM  Steward, S  Howard, TA  Mortier, NA  Kimble, AC  Aygun, B  Hankins, JS  Neale, GA  Ware, RE 
Citation: Flanagan JM, etal., Br J Haematol. 2012 Apr;157(2):240-8. doi: 10.1111/j.1365-2141.2012.09061.x. Epub 2012 Feb 24.
RGD ID: 11100007
Pubmed: PMID:22360576   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1365-2141.2012.09061.x   (Journal Full-text)

Sickle cell anaemia (SCA) is a severe debilitating haematological disorder associated with a high degree of morbidity and mortality. The level of fetal haemoglobin (HbF) is well-recognized as a critical laboratory parameter: lower HbF is associated with a higher risk of vaso-occlusive complications, organ damage, and early death. Hydroxycarbamide treatment can induce HbF, improve laboratory parameters, and ameliorate clinical complications of SCA but its mechanisms of action remain incompletely defined and the HbF response is highly variable. To identify pathways of hydroxycarbamide activity, we performed microarray expression analyses of early reticulocyte RNA obtained from children with SCA enrolled in the HydroxyUrea Study of Long-term Effects (NCT00305175) and examined the effects of hydroxycarbamide exposure in vivo. Hydroxycarbamide affected a large number of erythroid genes, with significant decreases in the expression of genes involved in translation, ribosome assembly and chromosome organization, presumably reflecting the daily cytotoxic pulses of hydroxycarbamide. Hydroxycarbamide also affected expression of numerous genes associated with HbF including BCL11A, a key regulator of baseline HbF levels. Together, these data indicate that hydroxycarbamide treatment for SCA leads to substantial changes in erythroid gene expression, including BCL11A and other potential signalling pathways associated with HbF induction.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BCL11AHumansickle cell anemia treatmentIDA  RGD 
Bcl11aRatsickle cell anemia treatmentISOBCL11A (Homo sapiens) RGD 
Bcl11aMousesickle cell anemia treatmentISOBCL11A (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bcl11a  (BCL11 transcription factor A)

Genes (Mus musculus)
Bcl11a  (BCL11 transcription factor A)

Genes (Homo sapiens)
BCL11A  (BCL11 transcription factor A)


Additional Information