Am J Blood Res 2012;2(2):119-127
Original Article
The involvement of Galectins in the modulation of the JAK/STAT pathway in
myeloproliferative neoplasia
Suzanne M Koopmans, Freek J Bot, Harry C Schouten, Jannie Janssen, Arienne MW van Marion
Department of Pathology of the Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Internal
Medicine division of Haematology of the Maastricht University Medical Centre, Maastricht, The Netherlands; Department of
Clinical Genetics of the University Hospital Maastricht, Maastricht, The Netherlands; Department of Pathology of the Haga
hospital, The Hague, The Netherlands; Department of Pathology of the VieCuri Medical Centre, Venlo, The Netherlands
Received April 16, 2012; accepted May 21, 2012; Epub May 25, 2012; Published June 15, 2012
Abstract: Background: In patients with myeloproliferative neoplasia (MPN) the development of fibrosis and increased vessel
density correlate with poor prognosis. The JAK2V617F mutation constitutively activates JAK2, which phosphorylates signal
transducer activator of transcription (STAT), up-regulating vascular endothelial growth factor (VEGF), which might be
responsible for angiogenesis in MPN. Galectins are involved in the development of fibrosis and angiogenesis and might also
be involved in activation of the JAK/STAT pathway in MPN. Methods: 106 MPN patients, 36 essential thrombocythemia (ET), 25
polycythemia vera (PV) and 45 primary myelofibrosis (PMF), were analyzed for the expression pattern of galectin-1, galectin-3,
pSTAT3, pSTAT5 and MVD by immunostaining of bone marrow biopsy sections followed by automated image analysis. The
JAK2 mutational status was analysed through real time PCR in blood samples. Results: The expression of galectin-1 was
significantly higher in all MPN patients compared to normal controls. Galectin-3 was expressed more in PV patients. MVD was
significantly higher in all MPN patients and correlated with galectin-1 and pSTAT5 expression. pSTAT5 expression showed a
trend of higher expression in patients carrying the JAK2V617F mutation as well as in PV patients. PMF patients and all
JAK2V617F positive patients showed a significantly higher pSTAT3 expression compared to control and ET patients.
Conclusion: The findings suggest the involvement of galectin-1 in MPN development, regardless of the subtype. Furthermore
involvement of galectin-3 in PV development, pSTAT5 in that of PV and JAK2V617F positive patients and angiogenesis, as well
as pSTAT3 is involved in the pathogenesis of PMF. (AJBR1204001).
Keywords: MPN, myeloproliferative neoplasia, galectin, JAK, STAT, angiogenesis, MVD
Address all correspondence to:
Dr. Suzanne M Koopmans
Department of Pathology
Maastricht University Medical Centre Postbus 5800
6202 AZ Maastricht, The Netherlands.
Tel: +31-(0)433874641
E-mail: s.koopmans@mumc.nl
Original Article
The involvement of Galectins in the modulation of the JAK/STAT pathway in
myeloproliferative neoplasia
Suzanne M Koopmans, Freek J Bot, Harry C Schouten, Jannie Janssen, Arienne MW van Marion
Department of Pathology of the Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Internal
Medicine division of Haematology of the Maastricht University Medical Centre, Maastricht, The Netherlands; Department of
Clinical Genetics of the University Hospital Maastricht, Maastricht, The Netherlands; Department of Pathology of the Haga
hospital, The Hague, The Netherlands; Department of Pathology of the VieCuri Medical Centre, Venlo, The Netherlands
Received April 16, 2012; accepted May 21, 2012; Epub May 25, 2012; Published June 15, 2012
Abstract: Background: In patients with myeloproliferative neoplasia (MPN) the development of fibrosis and increased vessel
density correlate with poor prognosis. The JAK2V617F mutation constitutively activates JAK2, which phosphorylates signal
transducer activator of transcription (STAT), up-regulating vascular endothelial growth factor (VEGF), which might be
responsible for angiogenesis in MPN. Galectins are involved in the development of fibrosis and angiogenesis and might also
be involved in activation of the JAK/STAT pathway in MPN. Methods: 106 MPN patients, 36 essential thrombocythemia (ET), 25
polycythemia vera (PV) and 45 primary myelofibrosis (PMF), were analyzed for the expression pattern of galectin-1, galectin-3,
pSTAT3, pSTAT5 and MVD by immunostaining of bone marrow biopsy sections followed by automated image analysis. The
JAK2 mutational status was analysed through real time PCR in blood samples. Results: The expression of galectin-1 was
significantly higher in all MPN patients compared to normal controls. Galectin-3 was expressed more in PV patients. MVD was
significantly higher in all MPN patients and correlated with galectin-1 and pSTAT5 expression. pSTAT5 expression showed a
trend of higher expression in patients carrying the JAK2V617F mutation as well as in PV patients. PMF patients and all
JAK2V617F positive patients showed a significantly higher pSTAT3 expression compared to control and ET patients.
Conclusion: The findings suggest the involvement of galectin-1 in MPN development, regardless of the subtype. Furthermore
involvement of galectin-3 in PV development, pSTAT5 in that of PV and JAK2V617F positive patients and angiogenesis, as well
as pSTAT3 is involved in the pathogenesis of PMF. (AJBR1204001).
Keywords: MPN, myeloproliferative neoplasia, galectin, JAK, STAT, angiogenesis, MVD
Address all correspondence to:
Dr. Suzanne M Koopmans
Department of Pathology
Maastricht University Medical Centre Postbus 5800
6202 AZ Maastricht, The Netherlands.
Tel: +31-(0)433874641
E-mail: s.koopmans@mumc.nl
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