Transcription factor Fli-1 expression by bone marrow cells in chronic myeloproliferative disorders is independent of an underlying JAK2 (V617F) mutation.
OBJECTIVE
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.


CONCLUSIONS
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.
Bock
Oliver
O
Institute of Pathology, Hannover Medical School, Hannover, Germany. bock.oliver@mh-hannover.de
Hussein
Kais
K
Neusch
Michael
M
Schlué
Jerome
J
Wiese
Birgitt
B
Kreipe
Hans
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008024:Ligands; D008840:Microfilament Proteins / Q000096:biosynthesis* / Q000502:physiology*; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000502:physiology*; D013920:Thrombocythemia, Essential / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism
C098179:FLII protein, human; D008024:Ligands; D008840:Microfilament Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D014157:Transcription Factors; C507924:JAK2 protein, human; D053614:Janus Kinase 2