Thesis (M.Sc.) - Cairo University - Faculty of Medicine - Department of Clinical and chemical pathology

Background: Acute myeloid leukemia (AML) is a heterogeneous group of diseases characterized by uncontrolled proliferation of hematopoietic progenitor cells with arrest of maturation and disruption of normal hematopoiesis. RUNX1 (Runt-related transcription factor 1) is a master regulator of definitive hematopoiesis where it regulates the differentiation of myeloid, megakaryocytic and lymphocytic lineage progenitors. RUNX1 is commonly disrupted by chromosomal translocations in hematological malignancies generating oncogenic fusion proteins or truncating RUNX1 that interfere with wild-type RUNX1. Genetic aberrations resulting in rearrangement of RUNX1, including generation of RUNX1 fusion genes, have been shown to be critical events in both myeloid and lymphoblastic acute leukemias. Aim of the work: is to detect the prevalence of RUNX1 gene alterations and its impact on clinical outcome in newly diagnosed AML patients. Various prognostic markers and other clinical and laboratory findings were studied in relation to RUNX1 gene alterations expressionPatients and methods: The current study was conducted on 77 newly diagnosed AML cases. Detection of RUNX1 alterations was done by florescence in-situ hybridization (FISH) technique. Results: The study revealed that RUNX1 abnormalities were detected by FISH in 41.6% of the studied patients including 20.8% were positive for RUNX1 translocations, 22.1% were positive for RUNX1 amplification and 5.2% were positive for RUNX1 deletion. RUNX1 deletion and DFS (Disease Free Survival) revealed a high statistically significant relation with p-value<0.001 with a mean of 3.033 months which indicates it carries the worst prognosis, while there was no statistically significant relation between RUNX1 abnormalities, RUNX1 translocations or RUNX1 amplification and DFS. Conclusion: inactivation of normal RUNX1 function is a potent key factor occurring early in the leukemogenic process and generally affects disease progression negatively. Therefore, targeting of RUNX1 has relevant significance as a new therapeutic strategy in AML

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