Thesis (Ph.D.) - Cairo University - National Cancer Institute - Department of Clinical Pathology

Background: Acute lymphoblastic leukemia (ALL) is a malignant transformation and proliferation of lymphoid progenitor cells in the bone marrow, blood and extramedullary sites. It is the most common leukemia in children. In ALL, TP53 mutations have been poorly investigated, mainly in children. Tumorsuppressor pathways such as TP53 function in part by reducing the angiogenic potential of transformed cells. Limiting angiogenesis by TP53 occurs through the dual action of inhibiting proangiogenic signals and increasing production of angiostatic factors. To our knowledge this issue was poorly investigated in Egypt, Middle East and in international publications. Objective: In this study we investigated the impact of TP53 gene mutation and angiogenesis on the induction of remission in Egyptian children newly diagnosed of having ALL. Patients and methods: This study included 40 de novo Egyptian pediatric ALL patients referred from the pediatric oncology outpatient clinics in NCI-Cairo University in the period between May 2015 to June 2016. Bone marrow aspiration (BMA) and trephine biopsy (BMB) were obtained from all patients at diagnosis. Immunohistochemistry (IHC) will be carried out using anti CD- 34 monoclonal antibodies to study microvascular density (MVD) as marker of angiogenesis and BM aspirates were cultured, harvested and prepared for fluorescent in situ hybridization (FISH) to study TP53. All patients received total 15 induction therapy and were assessed at day 42 (end of phase 2 induction)

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