Implications and Potential Therapeutic Targeting of Insulin-Like Growth Factor Type 1 Receptor (IGF-IR) in Adulthood Acute Lymphoblastic Leukemia

Background: A greater understanding of the pathogenesis of malignancy has led to the development of novel therapies designed to target aberrant molecular pathways that characterize and distinguish cancer cells from normal tissue. Small molecules are being designed to interfere with specific steps along the deregulated signaling cascade from the cytoplasmic membrane to the nucleus. Viable targets include growth factor receptors and their downstream second messengers, modulators of the cell cycle or apoptosis, regulators of protein trafficking and degradation and transcription regulators. Many reviews had discussed the small molecule signal transduction inhibitors in various stages of development and address the strategic issues relating to clinical trial design with these novel targeted agents. Aim of Work: To verify the Insulin-Like Growth Factor Type 1 Receptor (IGF-IR) and its impact on proliferation of lymphoblasts in Adulthood Acute Lymphoblastic leukemia (ALL). Bone marrow samples from 30 patients with ALL were examined along with 10 healthy donors as controls, a quantitative real time reverse transcriptase polymerase chain reaction (Real time R.T PCR) used to evaluate the concentration of (IGF-IR) correlated with the blast concentration in marrow samples. In our assay (IGF-IR) appeared to have higher to lower expression rate in turn from ALL (27.897) if compared with normal controls (37.883) (p<0.01). This work was carried out to prive the effect of IGF-IR on hematopoie- tic cells in ALL and its relation to the diseases progress. Patients and Methods: The expression of IGF-IR was analyzed in 30 patients with ALL, The patient work over a 3 month's period from February 2008 to May 2008. They were 18 males and 12 females with a male to females' ratio 1.5: 1.0. Their ages ranged from 12 - 51 years. All patients were diagnosed as ALL by the routine diagnosis in Egypt national cancer institute with 10 normal age and sex matched healthy controls using a Real-Time Quantitative Reverse- Transcriptase Polymerase Chain Reaction (qRT-PCR) to assess the possible relation, association or correlation between IGF-IR expression and ALL clinical and laboratory features at diagnosis. Results: IGF-IR was expressed in all 30 patients with ALL; the expression levels of IGF-IR was significantly higher in newly diagnosed patients than in patients in complete remission (CR) and controls (p<0.001). There were statistically significant differences in the expression of IGF-IR between patients with blast concentration. Conclusion: IGF-1R seems to play a crucial role in patients with Adulthood and over expression of (IGF-IR) existed in hematopoietic cells in ALL marrows which appeared to be contributed to disease progress. 1- Over expression of (IGF-IR) existed in hematopoietic cells in ALL marrows which appeared to be contributed to disease progress. 2- Over expressed in our patient. 3- Over express contributed to disease progress.