FoxO3a and PU.1 in Acute Lymphoblastic Leukemia

Not yet recruiting

• Conditions: Acute Lymphoblastic Leukemia
• Interventions: Other: complete blood count

• Registration Number: NCT04092348
• Lead Sponsor: Assiut University

Brief Summary

Acute Lymphoblastic Leukemia (ALL) is one of the four major types of leukemia which is common in both children and adolescents; however, it is the most common pediatric malignancy diagnosed in children younger than 20 years .The disease pathogenesis results from blockade at any stages of normal lymphoid differentiation with uncontrolled proliferation of lymphoid cells. According to the World Health Organization (WHO) definition, ALL is categorized in B-Lymphoblastic Leukemia (B-ALL) And T-Lymphoblastic Leukemia (T-ALL), originated from B- and T-Lineage lymphoid precursor cells, respectively.

Detailed Description

Proto-oncogenes and tumor suppressor genes are the most important genes involved in leukemogenesis , which their alterations disrupt normal regulatory processes such as self-renewal, proliferation, differentiation and apoptosis in target cells. Among those genes FoxO3a gene and PU.1 gene.

FoxO(Fork head box ,class O) transcription factors function as a tumor suppressor gene and are important for stem cell maintenance.They are key regulators of the cellular differentiation, growth, survival, cell cycle, metabolism, and cellular stress. There are four members of the foxO transcription factors in humans : foxO1, foxO3a, foxO4, foxO6 .FoxO3a is expressed in various tissues including B - and T-lymphoid cells. Over expression of FoxO3a in B and T cell lines induces cell cycle arrest in G1 phase , so it inhibits cell proliferation . FoxO3a is an important target of PI3K/AKT signaling pathway,which is hyperactivated in various types of cancers .Hyperactivation of this pathway in leukemia leads to inactivation of foxO3a in leukemic cells and enhances tumor growth .

PU .1(Purine-rich box 1) is a member of the E26 transformation-specific (ETS) Family . Normal hematopoiesis is securely controlled by asmall number of lineage-specific transcription factors, so that the disturbed expression or function of this group may be involved in the development of leukemia . PU.1 plays an important role in hematopiotic stem cell (HSC) self renewal and in myeloid and B-lymphoid differentiation. It controls the expression of several genes involved in hematopoiesis.

Study Timeline

• Study First Submitted: 2019-09-14
• Study First Submitted QC: 2019-09-14
• Study First Posted: 2019-09-17
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-05
• Last Update Posted: 2023-02-08
• Study Start: 2023-08-01
• Primary Completion: 2024-03-30
• Study Completion: 2024-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 53

Inclusion Criteria

• children aged 2-17 years and diagnosed as new cases of acute lymphoblastic leukemia

Exclusion Criteria

1. age more than 17 years
2. presence of other hematological disorders, history of other malignancies ,or relapsed ALL
3. patients under chemotherapy or radiotherapy

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
control group	complete blood count	healthy age- and sex-matched children without ahistory of any malignancies
study group	complete blood count	children aged 2-17 years and diagnosed as new cases of acute lymphoblastic leukemia

Primary Outcome Measures

Name	Time	Method
FoxO3a and PU.1 levels in acute lymphoblastic leukemia	2 years	detection of the mean difference in FoxO3a and PU.1 expression levels between cases and controls