High telomerase activity in granulocytes from clonal polycythemia vera and essential thrombocythemia

Abstract

Essential thrombocythemia (ET) and polycythemia vera (PV) are chronic myeloproliferative disorders that share the involvement of a multipotent progenitor cell and dominance of the transformed clone over normal hematopoiesis. On the other hand, the heterogeneity of these diseases with respect to clonal development from a common progenitor has been well established.

Clonal granulocytes in polycythaemia vera and essential thrombocythaemia have shortened telomeres

“…We then determined the TRF lengths of haemopoietic cells from 22 women with CMPDs (nine with PV and 13 with ET), seven of which had polyclonal granulopoiesis (Ferraris et al, 2005). Patients with clonal PMNs had a mean DTRF of 4AE6 kb, while those with polyclonal granulopoiesis had a mean DTRF of 0AE44 kb (P < 0AE0015).…”

“…A total of 22 women with a diagnosis of PV or ET and heterozygous at the X-linked HUMARA locus (Ferraris et al, 2005) were analysed. Haematological diagnosis was according to the Polycythemia Vera Study Group criteria (Murphy et al, 1986), and likely causes of secondary polycythaemia or reactive thrombocytosis were carefully excluded.…”

“…In a recent report we provided evidence of a high telomerase activity (TA) in granulocytes from women with clonal PV and ET, while clinically undistinguishable subjects with polyclonal granulopoiesis had normal TA (Ferraris et al, 2005).…”

“…We therefore decided to analyse telomere lengths in haemopoietic cell populations from the same group of women with PV and ET previously tested for TA, and with either clonal or polyclonal granulopoiesis, as ascertained by XCIP (Ferraris et al, 2005).…”

Human telomerase is regulated by erythropoietin and transforming growth factor-β in human erythroid progenitor cells

“…The fact that high telomerase activity has been described in granulocytes from clonal polycythemia vera supports this hypothesis. 18 The fact that JAK2/STAT5 is an important regulator of hTERT may also have important consequences in the biology of acute leukemia cells. Indeed, previous studies have established that, in acute myeloid leukemia (AML), the JAK/STAT pathway is a major target of various oncogenic products including leukemic fusion proteins and activated tyrosine kinase receptors.…”