الفهرس 
Impact of Notch1 Signaling Pathway on Clinical Course of Pediatric T-cell Acute Lymphoblastic Leukemia
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Abstract
Acute Lymphoblastic Leukemia (ALL) represents the most commonly diagnosed cancer in
children. T-cell Acute Lymphoblastic Leukemia (T-cell ALL) accounts for around 10-15% of
pediatric ALL cases and 25% of adult cases. Constitutive activation of Notch signaling pathway
takes place, as a result of NOTCH1 activating mutations, in over 60 % of T-ALL cases. Despite
the remarkable improvement that the world has witnessed over the last half-century in the
prognosis of ALL, relapse is still a major challenge. Also, the increasing percentage of patients
suffering from treatment-related toxicities or chemotherapeutic resistance and recurrence has
indicated the inaccuracy of the currently used risk allocation schemes, which consequently
explains the necessity of a more reliable assessment approach of the leukemic status.
Consequently, a deeper understanding of T-ALL biology at the molecular level is urgently
needed to facilitate the identification of novel diagnostic and prognostic biomarkers and
therapeutic targets that can ultimately enable early detection, targeted therapy with minimal side
effects, and hence a better prognosis. More attention has been paid towards investigating the
direct and indirect regulatory roles that NOTCH1 plays in order to promote leukemogenesis. The
oncogenic microRNA miR-21 has been implicated in several hematological malignancies and
solid tumors. Its oncogenic role in T-ALL is being exhibited through targeting the tumorsuppressive programmed cell death protein 4 (PCDP4). Its aberrant expression has also been
associated with a poor prognosis. On the other hand, miR-193b-3p, or miR-193b, is a wellcharacterized tumor-suppressive microRNA that is usually downregulated in a wide range of
cancers. In T‐ cell acute lymphoblastic leukemia, miR‐ 193b‐ 3p was also found to be
repressed, and its repression was negatively associated with the proto‐ oncogene MYB
expression. Its downregulation was also found to be associated with unfavorable prognostic
features. Although the Notch-regulated long non-coding RNA, LUNAR1, has been demonstrated
to be among the most prominently dysregulated lncRNAs in T-ALL cases, the association of its
expression levels in the peripheral blood of patients with the clinicopathological features and/or
prognosis has not been assessed yet