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

Ferraris, Anna Maria; Mangerini, Rosa; Pujić, Natalija; Racchi, Omar; Rapezzi, Davide; Gallamini, Andrea; Casciaro, Salvatore; Gaetani, Gian Franco

doi:10.1182/blood-2004-06-2375

Cited by 13 publications

(10 citation statements)

References 21 publications

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“…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).…”

Section: Resultsmentioning

confidence: 99%

“…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.…”

Section: Methodsmentioning

confidence: 99%

“…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).…”

mentioning

confidence: 99%

“…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).…”

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confidence: 99%

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Clonal granulocytes in polycythaemia vera and essential thrombocythaemia have shortened telomeres

et al. 2005

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The purpose of this study was to evaluate telomere length in peripheral blood granulocytes and mononuclear cells collected from 22 women with polycythaemia vera (PV) and essential thrombocythaemia (ET). PV and ET are chronic myeloproliferative diseases whose heterogeneity of stem cell origin and clonal development has been established through analysis of X-chromosome inactivation patterns. The results from clonality assay and determination of telomere length show that only clonal granulocytes have shortened telomeres

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Clonal granulocytes in polycythaemia vera and essential thrombocythaemia have shortened telomeres

et al. 2005

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2007

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Telomerase catalytic subunit (hTERT) exerts important cellular functions including telomere homeostasis, genetic stability, cell survival and perhaps differentiation. However, the nature of external or internal signals, which regulate hTERT expression in tissues, remains poorly understood. Thus, whereas it has been described that hTERT gene is regulated along the differentiation of primitive myeloid progenitors, the effect of specific cytokines on telomerase expression in each myeloid lineage is currently unknown. Based on these considerations, we have investigated hTERT expression in erythroid cells treated with erythropoietin (EPO) and transforming growth factor b (TGFb), as putative positive and negative regulators, respectively. We describe here that EPO activates hTERT gene transcription in in vitro-expanded primary erythroid precursors as well as in UT7 erythroleukemia cells. In UT7 cells, this study shows also that EPO acts through a JAK2/STAT5/c-myc axis. In contrast, TGFb blocks EPO signaling downstream of c-myc induction through a Smad3-dependent mechanism. Finally, hTERT appears to be efficiently regulated by EPO and TGFb in an opposite way in erythropoietic cells, arguing for a role of telomerase in red blood cell production.

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Novel approaches in myelofibrosis

Koschmieder

2024

HemaSphere

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Myelofibrosis (MF) is a clonal myeloid neoplasm characterized by bone marrow fibrosis, splenomegaly, and disease‐associated symptoms, as well as increased mortality, due to thrombosis, severe bleeding, infections, or progression to acute leukemia. Currently, the management of MF patients is tailored according to risk scores, with higher‐risk (intermediate‐2 and high‐risk) patients being assessed for allogeneic stem cell transplantation, which remains the only potentially curative treatment option. On the other hand, lower risk (low‐ and intermediate‐1 risk) patients who are symptomatic may be treated with JAK inhibitors or other drugs. However, none of these drug treatments have induced relevant rates of durable complete remissions, and, therefore, novel treatments are needed to improve the long‐term outcomes of MF patients. This review summarizes current preclinical and clinical approaches to MF therapy, including novel drug combinations involving JAK inhibitors and innovative monotherapies. These drugs target transcription, nuclear export, survival pathways, or various intracellular pathways, ranging from JAK‐STAT signaling to PI3‐Kinase, TP53, PIM1, or S100A8/A9/toll‐like receptor pathways. Also, extracellular targeting using interferon, calreticulin mutant‐specific antibodies, and other immunotherapeutic approaches are discussed, as well as various antifibrotic strategies. In addition, preclinical approaches that target individual mutated clones, for example, by mutation‐specific JAK2V617F inhibitors or DNA repair pathway inhibitors, are presented. Finally, current efforts of generating novel endpoints for clinical trials aim more at disease modification and overall survival than at improvements of splenomegaly or symptoms. Together, the new generations of clinical trials promise to offer substantial improvements in the management of MF patients and long‐term disease control.

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

Cited by 13 publications

References 21 publications

Clonal granulocytes in polycythaemia vera and essential thrombocythaemia have shortened telomeres

Clonal granulocytes in polycythaemia vera and essential thrombocythaemia have shortened telomeres

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

Novel approaches in myelofibrosis

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