Long non-coding RNAs (lncRNAs) are emerging as key regulators of gene expression in normal and cancer cells by recruiting chromatin remodeling complexes. Despite their characterization in several tumor types, little is known about the role of lncRNAs in malignant hematopoiesis. In particular, lncRNAs expression has never been investigated in cells from primary myelofibrosis (PMF) patients. PMF is a Philadelphia negative chronic Myeloproliferative Neoplasm (MPN) that originates from deregulated clonal proliferation of hematopoietic stem cell associated with overproduction of mature blood cells. Molecular basis underlying MPN pathogenesis were partially unraveled in 2005-2006 with the identification of somatic mutations of JAK2 and MPL, after which many other mutations were identified. Recently, several new molecular pathogenetic mechanisms were proposed, such as the aberrant expression of coding and non-coding RNAs. In order to identify other molecular abnormalities harbored by PMF patients, we investigated the expression of CDKN2B-antisense (ANRIL), MEG3 and WT1-antisense lncRNAs, previously described as potentially involved in hematological malignancies, in CD34+ cells from PMF patients. The results evidence that the majority of PMF samples displays a co-upregulation of WT1 and its antisense RNA compared to controls. These samples also show an increased MEG3 expression. In these patients, we found a correlation with high Dynamic International Prognostic Scoring System (DIPPS) plus score and elevated number of circulating CD34+ cells. Moreover, the expression pattern of CDKN2B/ANRIL distinguishes a group of patients characterized by an upregulation of CDKN2B, and, among these, a subgroup with downregulated ANRIL. Of note, this group of patients was characterized by a higher grade of bone marrow fibrosis and by the presence of JAK2V617F mutation. Our results suggest that a deregulated expression of these lncRNAs could play a role in PMF pathogenesis and progression.

Abnormal expression of WT1-as, MEG3 and ANRIL long non-coding RNAs in primary myelofibrosis and their clinical correlates / Pennucci, Valentina; Zini, Roberta; Norfo, Ruggiero; Guglielmelli, P.; Bianchi, Elisa; Salati, Simona; Sacchi, G.; Prudente, Z.; Tenedini, Elena; Ruberti, S.; Rontauroli, S.; Paoli, C.; Fanelli, T.; Mannarelli, C.; Tagliafico, E.; Vannucchi, A. M.; Ferrari, S.; Manfredini, R.. - STAMPA. - -:(2013), pp. 28-28. ((Intervento presentato al convegno XV Congresso AIBG tenutosi a Arcavacata di Rende (CS) nel 27-28 Settembre 2013.

Abnormal expression of WT1-as, MEG3 and ANRIL long non-coding RNAs in primary myelofibrosis and their clinical correlates

PENNUCCI, VALENTINA;ZINI, Roberta;NORFO, RUGGIERO;BIANCHI, Elisa;SALATI, Simona;TENEDINI, Elena;Tagliafico E.;
2013

Abstract

Long non-coding RNAs (lncRNAs) are emerging as key regulators of gene expression in normal and cancer cells by recruiting chromatin remodeling complexes. Despite their characterization in several tumor types, little is known about the role of lncRNAs in malignant hematopoiesis. In particular, lncRNAs expression has never been investigated in cells from primary myelofibrosis (PMF) patients. PMF is a Philadelphia negative chronic Myeloproliferative Neoplasm (MPN) that originates from deregulated clonal proliferation of hematopoietic stem cell associated with overproduction of mature blood cells. Molecular basis underlying MPN pathogenesis were partially unraveled in 2005-2006 with the identification of somatic mutations of JAK2 and MPL, after which many other mutations were identified. Recently, several new molecular pathogenetic mechanisms were proposed, such as the aberrant expression of coding and non-coding RNAs. In order to identify other molecular abnormalities harbored by PMF patients, we investigated the expression of CDKN2B-antisense (ANRIL), MEG3 and WT1-antisense lncRNAs, previously described as potentially involved in hematological malignancies, in CD34+ cells from PMF patients. The results evidence that the majority of PMF samples displays a co-upregulation of WT1 and its antisense RNA compared to controls. These samples also show an increased MEG3 expression. In these patients, we found a correlation with high Dynamic International Prognostic Scoring System (DIPPS) plus score and elevated number of circulating CD34+ cells. Moreover, the expression pattern of CDKN2B/ANRIL distinguishes a group of patients characterized by an upregulation of CDKN2B, and, among these, a subgroup with downregulated ANRIL. Of note, this group of patients was characterized by a higher grade of bone marrow fibrosis and by the presence of JAK2V617F mutation. Our results suggest that a deregulated expression of these lncRNAs could play a role in PMF pathogenesis and progression.
XV Congresso AIBG
Arcavacata di Rende (CS)
27-28 Settembre 2013
Pennucci, Valentina; Zini, Roberta; Norfo, Ruggiero; Guglielmelli, P.; Bianchi, Elisa; Salati, Simona; Sacchi, G.; Prudente, Z.; Tenedini, Elena; Ruberti, S.; Rontauroli, S.; Paoli, C.; Fanelli, T.; Mannarelli, C.; Tagliafico, E.; Vannucchi, A. M.; Ferrari, S.; Manfredini, R.
Abnormal expression of WT1-as, MEG3 and ANRIL long non-coding RNAs in primary myelofibrosis and their clinical correlates / Pennucci, Valentina; Zini, Roberta; Norfo, Ruggiero; Guglielmelli, P.; Bianchi, Elisa; Salati, Simona; Sacchi, G.; Prudente, Z.; Tenedini, Elena; Ruberti, S.; Rontauroli, S.; Paoli, C.; Fanelli, T.; Mannarelli, C.; Tagliafico, E.; Vannucchi, A. M.; Ferrari, S.; Manfredini, R.. - STAMPA. - -:(2013), pp. 28-28. ((Intervento presentato al convegno XV Congresso AIBG tenutosi a Arcavacata di Rende (CS) nel 27-28 Settembre 2013.
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