OBJECTIVES: Friend leukemia integration-1 (Fli-1), a member of the Ets gene family of transcription factors, has been demonstrated to be a target of a leukaemia inducing virus in mice, and is known to be part of a fusion gene in Ewings' sarcoma in humans. Wild-type Fli-1 is involved in lineage commitment of megakaryocytes and myeloid progenitors through induction of Janus kinases (JAKs) following ligand binding to cytokine and growth factor receptors. Proliferation of atypical megakaryocytes is a predominant histopathological feature in Philadelphia chromosome negative chronic myeloproliferative disorders (Ph(-) CMPD) and a potential aberrant expression of Fli-1 has not been investigated so far. METHODS: Fli-1 expression was investigated by real-time RT-PCR and immunohistochemistry in bone marrow cells derived from Ph(-) CMPD (n = 80) and non-neoplastic haematopoiesis (n = 21) following determination of the JAK2 status. RESULTS: Fli-1 mRNA expression was significantly higher in Essential thrombocythaemia (ET) with JAK2 (V617F) compared with other Ph(-) CMPD and control (P < 0.001). By immunohistochemistry, Fli-1 protein could be detected in nuclei of atypical megakaryocytes in Ph(-) CMPD and, less accentuated, in non-neoplastic megakaryocytes. Fli-1 protein expression by myeloid progenitors was considerably heterogenous in Ph(-) CMPD independent of an underlying JAK2 (V617F) mutation and without notable differences to non-neoplastic haematopoiesis. CONCLUSION: Fli-1 is rather constitutively expressed by bone marrow cells in Ph(-) CMPD independent of the underlying JAK2 status. The overall stronger labelling for Fli-1 in megakaryocytes in Ph(-) CMPD most likely reflects the degree of polyploidisation but aberrant activation of nuclear target genes can not be excluded.
OBJECTIVES:Friend leukemia integration-1 (Fli-1), a member of the Ets gene family of transcription factors, has been demonstrated to be a target of a leukaemia inducing virus in mice, and is known to be part of a fusion gene in Ewings' sarcoma in humans. Wild-type Fli-1 is involved in lineage commitment of megakaryocytes and myeloid progenitors through induction of Janus kinases (JAKs) following ligand binding to cytokine and growth factor receptors. Proliferation of atypical megakaryocytes is a predominant histopathological feature in Philadelphia chromosome negative chronic myeloproliferative disorders (Ph(-) CMPD) and a potential aberrant expression of Fli-1 has not been investigated so far. METHODS:Fli-1 expression was investigated by real-time RT-PCR and immunohistochemistry in bone marrow cells derived from Ph(-) CMPD (n = 80) and non-neoplastic haematopoiesis (n = 21) following determination of the JAK2 status. RESULTS:Fli-1 mRNA expression was significantly higher in Essential thrombocythaemia (ET) with JAK2 (V617F) compared with other Ph(-) CMPD and control (P < 0.001). By immunohistochemistry, Fli-1 protein could be detected in nuclei of atypical megakaryocytes in Ph(-) CMPD and, less accentuated, in non-neoplastic megakaryocytes. Fli-1 protein expression by myeloid progenitors was considerably heterogenous in Ph(-) CMPD independent of an underlying JAK2 (V617F) mutation and without notable differences to non-neoplastic haematopoiesis. CONCLUSION:Fli-1 is rather constitutively expressed by bone marrow cells in Ph(-) CMPD independent of the underlying JAK2 status. The overall stronger labelling for Fli-1 in megakaryocytes in Ph(-) CMPD most likely reflects the degree of polyploidisation but aberrant activation of nuclear target genes can not be excluded.
Authors: Steven M Kornblau; Yi Hua Qiu; Nianxiang Zhang; Neera Singh; Stefan Faderl; Alessandra Ferrajoli; Heather York; Amina A Qutub; Kevin R Coombes; Dennis K Watson Journal: Blood Date: 2011-09-13 Impact factor: 22.113