Bone marrow glycophorin-positive erythroid cells of myelodysplastic patients responding to high-dose rHuEPO therapy have a different gene expression pattern from those of nonresponders.
The main clinical problems of low-risk patients with myelodysplastic syndromes (MDS), as defined by the International Prognostic Scoring System, are infections and the need for frequent transfusions due to ineffective myelopoiesis and peripheral blood cytopenia. Promising results in treating MDS-related anemia have been obtained using high-dose recombinant human erythropoietin (rhEPO). To evaluate the molecular basis of the response to rhEPO, we used commercially available macro-arrays to investigate gene expression profiles in the glycophorin-expressing (Gly+) bone marrow (BM) erythroid cells of five responders (ERs) and five non-responders (ENRs) to rhEPO treatment. The cells were separated by means of positive selection using an immunomagnetic procedure, after which flow cytometry showed that their purity was more than 97% in all cases. The array data were validated by means of real time RT-PCR. The results showed that the genes responsible for proliferation/differentiation and DNA repair/stability were repressed in the BM Gly+ erythroid cells of the ENRs, but almost normally expressed in the ERs. Furthermore, the expression of genes involved in signal transduction suggested that the activity of the MAPK signaling pathway is inhibited in ERs. The different gene expression profiles of ERs and ENRs may provide a basis for early gene testing as a means of predicting the response to rhEPO of MDS patients with low endogenous EPO levels.
Cortelezzi
Agostino
A
Hematology-Bone Marrow Transplant Unit, Fondazione Ospedale Maggiore Maggiore Policlinico, Mangiagalli, Regina Elena IRCCS, Milan. agostino.cortelezzi@unimi.it
Colombo
Gualtiero
G
Pellegrini
Caterina
C
Silvestris
Ilaria
I
Moronetti Mazzeo
Lorenza
L
Bosari
Silvano
S
Lambertenghi Deliliers
Giorgio
G
Fracchiolla
Nicola Stefano
NS
D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000378:metabolism*; D016000:Cluster Analysis; D015536:Down-Regulation / Q000187:drug effects; D041905:Erythroid Cells / Q000378:metabolism*; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006021:Glycophorins / Q000378:metabolism*; D006801:Humans; D008297:Male; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011994:Recombinant Proteins; D015854:Up-Regulation / Q000187:drug effects
D006021:Glycophorins; D011994:Recombinant Proteins; D004921:Erythropoietin