الفهرس 
The prevalence of the RUNX1 gene alterations in de novo acute myeloid leukemia using fluorescence in situ hybridization
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Abstract
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 expression.
Patients 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.