Variation of PDGF, TGFbeta, and bFGF levels in essential thrombocythemia patients treated with anagrelide.
We studied 15 patients with essential thrombocythemia (ET) before treatment and after normalization of platelet count by anagrelide. Significantly increased plasma levels of PDGF, TGFbeta, and bFGF were found. Patients with mild reticulin fibrosis in bone marrow had higher PDGF levels. During treatment, plasma TGFbeta and bFGF levels remained elevated in most patients (P < 0.0001 and P < 0.01, respectively). Intraplatelet PDGF levels were low before treatment (P < 0.006) and normal on hematological remission, without relation with the presence or absence of reticulin fibrosis in bone marrow. Intraplatelet TGFbeta levels were normal regardless of the platelet count. Intraplatelet bFGF levels were raised before (P < 0.001) and during treatment (P < 0.01). By immunostaining, TGFbeta and bFGF were seen in megakaryocytes and lymphocytes with a similar pattern of intensity in patients and controls, suggesting that other cells might also contribute to the raised plasma values. We believe that the plasma increment of these cytokines suggests that they play a role in the pathogenesis of ET. The normal PDGF plasma level found during treatment may be in relation with the platelet count. However, the persistent increase of TGF-beta in plasma and bFGF both in plasma and platelets may indicate dysregulation of cytokine synthesis in TE.
Sección Hematología Investigación, Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, Combatientes de Malvinas 3150, 1427 Buenos Aires, Argentina.
P R
PR
Lev
R F
RF
Marta
P
P
Vassallu
F C
FC
Molinas
D000293:Adolescent; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood*; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010976:Platelet Count; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011799:Quinazolines / Q000627:therapeutic use*; D012155:Reticulin / Q000032:analysis; D013922:Thrombocytosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000097:blood*
D010975:Platelet Aggregation Inhibitors; D010982:Platelet-Derived Growth Factor; D011799:Quinazolines; D012155:Reticulin; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; C021139:anagrelide