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Transcription factor Fli-1 expression by bone marrow cells in chronic myeloproliferative disorders is independent of an underlying JAK2 (V617F) mutation
- Source :
- European Journal of Haematology. 77:463-470
- Publication Year :
- 2006
- Publisher :
- Wiley, 2006.
-
Abstract
- 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.
- Subjects :
- Adult
Myeloid
medicine.medical_treatment
Receptors, Cytoplasmic and Nuclear
Bone Marrow Cells
Biology
Ligands
Fusion gene
Growth factor receptor
hemic and lymphatic diseases
medicine
Humans
Transcription factor
Aged
Aged, 80 and over
Cell Nucleus
Myeloproliferative Disorders
Microfilament Proteins
fungi
Hematology
General Medicine
Janus Kinase 2
Middle Aged
Haematopoiesis
medicine.anatomical_structure
Cytokine
Gene Expression Regulation
Mutation
Immunology
Trans-Activators
Cancer research
Bone marrow
Janus kinase
Thrombocythemia, Essential
Transcription Factors
Subjects
Details
- ISSN :
- 16000609 and 09024441
- Volume :
- 77
- Database :
- OpenAIRE
- Journal :
- European Journal of Haematology
- Accession number :
- edsair.doi.dedup.....fe44043b90ac35f80612c2af70ba8ccf