FoxO3a and PU.1 in Acute Lymphoblastic Leukemia

Sponsor
Assiut University (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT04092348
Collaborator
(none)
100
17

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Other: complete blood count

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 Design

Study Type:
Observational
Anticipated Enrollment :
100 participants
Observational Model:
Other
Time Perspective:
Cross-Sectional
Official Title:
Value of FoxO3a and PU.1 Expression in Pediatric Acute Lymphoblastic Leukemia
Anticipated Study Start Date :
Aug 1, 2022
Anticipated Primary Completion Date :
Mar 30, 2023
Anticipated Study Completion Date :
Dec 30, 2023

Arms and Interventions

Arm Intervention/Treatment
study group

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

Other: complete blood count
total RNA is isolated from fresh blood samples RNA is converted into complementary DNA c.DNA cDNA is then analysed by quantitatine Real Time PCR(qRT-PCR) to evaluate the relative expression levels of FoxO3a, PU.1 genes and TATA-binding protein (TBP) ,as an endogenous control gene.
Other Names:
  • bone marrow aspirate
  • control group

    healthy age- and sex-matched children without ahistory of any malignancies

    Other: complete blood count
    total RNA is isolated from fresh blood samples RNA is converted into complementary DNA c.DNA cDNA is then analysed by quantitatine Real Time PCR(qRT-PCR) to evaluate the relative expression levels of FoxO3a, PU.1 genes and TATA-binding protein (TBP) ,as an endogenous control gene.
    Other Names:
  • bone marrow aspirate
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Years to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Assiut University

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    MRA Youb, principal investigator, Assiut University
    ClinicalTrials.gov Identifier:
    NCT04092348
    Other Study ID Numbers:
    • madonna
    First Posted:
    Sep 17, 2019
    Last Update Posted:
    Feb 16, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 16, 2022