Aberrant expression of insulin-like growth factor-2 (IGF-2) in Philadelphia chromosome negative chronic myeloproliferative disorders.
Philadelphia chromosome negative chronic myeloproliferative disorders (Ph- CMPD) comprise haematopoietic stem cell disorders with currently unknown underlying molecular defect. Insulin-like growth factor 2 (IGF-2) is an imprinted gene that is known to be involved in the regulation of normal cell growth and that is overexpressed by a variety of tumors. The expression of IGF-2 in bone marrow cells is largely unknown. In order to elucidate gene expression level, protein expression pattern, and a potential role of IGF-2 in the pathogenesis of Ph- CMPD, we quantitatively analyzed the expression of the IGF-2 gene in bone marrow cells of 69 cases with Ph- CMPD and 31 control cases by applying real-time RT-PCR. IGF-2 gene expression in idiopathic myelofibrosis (IMF) was significantly increased by up to 11-fold as compared to the control group (P < 0.0001). IMF also expressed higher IGF-2 gene level as compared to essential thrombocythaemia (ET) and polycythaemia vera (PV) (P < 0.0001, P = 0.005, respectively). Paranuclear IGF-2 protein could be demonstrated in IMF, ET, and PV exclusively in megakaryocytes and myeloid progenitor cells in contrast to undetectable IGF-2 protein in control cases. We conclude that overexpression of the IGF-2 gene is a pathogenic feature in IMF. In addition, an abundant translational and post-translational processing could explain the accumulation of IGF-2 protein detectable in all Ph- CMPD entities in contrast to non-neoplastic haematopoiesis. We conclude that IGF-2 represents a new molecular target for evaluation of underlying fundamental pathomechanisms in Ph- CMPD.
Bock
Oliver
O
Institute of Pathology, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625, Germany. bock.oliver@mh-hannover.de
Tessema
Mathewos
M
Serinsöz
Ebru
E
von Wasielewski
Reinhard
R
Büsche
Guntram
G
Kreipe
Hans
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002908:Chronic Disease; D017931:DNA Primers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D007335:Insulin-Like Growth Factor II