Expression of type 1 insulin-like growth factor receptor in marrow nucleated cells in malignant hematological disorders: correlation with apoptosis

Abstract

To verify the expression of type 1 insulin-like growth factor receptor (IGF-IR) and its impact on hematopoietic cells apoptosis in myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML), marrow samples from 16 patients with MDS and 16 patients with AML were examined along with 16 healthy donors as controls. Immunocytochemical methods (alkaline phosphatase anti-alkaline phosphatase) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (fluorescence) were used simultaneously on nucleated cell cytospins. The ratio of IGF-IR positive cells and apoptotic cells as well as the relationship between them were then analyzed separately. A quantitative real-time reverse transcriptase-polymerase chain reaction (PCR) was administrated for six MDS cases and two normal controls to validate IGF-IR expression detected by immunochemistry. In our assay, IGF-IR appeared to have higher to lower expression rate in turn from AML (86.8+/-13.8%) to MDS (56.8+/-14.3%) and then to normal controls (40.4+/-9.6%) (P<0.01 between each group). In MDS nucleated cells, IGF-IR showed stronger expression in refractory anemia with excess blasts (RAEB)/RAEB in transformation/chronic myelomonocytic leukemia subgroup when compared to RA/RA with ringed sideroblasts cases (64.1+/-3.2 vs 53.5+/-16.2%) (P>0.05). Nucleated cells from MDS marrow underwent more apoptosis (5.4+/-3.0%) than that in normal marrow (1.2+/-0.9%) (P<0.01) and AML marrow (0.3+/-0.4%) (also, P<0.01 between each compared group). For both AML and MDS cases, apoptotic signals presented mainly in individual IGF-IR negative cells (9.0+/-4.8%) and less so in IGF-IR positive cells (1.4+/-2.4%) (P<0.01). When analyzed by groups, cell number with IGF-IR expression showed a negative correlation to apoptotic cells amount (r=-0.852; P<0.01) but positive correlation to their blast count (r=0.677; P<0.01). Outcome from real-time quantitative PCR appeared to have a trend of enhanced IGF-IR expression in advanced MDS subtypes. In conclusion, overexpression of IGF-IR existed in hematopoietic cells in MDS and AML marrows, which appeared to be contributed to disease progress.