FoxO3a and PU.1 in Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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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
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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.

Official Title
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Value of FoxO3a and PU.1 Expression in Pediatric Acute Lymphoblastic Leukemia

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Other: complete blood count


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: children aged 2-17 years and diagnosed as new cases of acute lymphoblastic leukemia Exclusion Criteria: age more than 17 years presence of other hematological disorders, history of other malignancies ,or relapsed ALL patients under chemotherapy or radiotherapy

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| study group<br>children aged 2-17 years and diagnosed as new cases of acute lymphoblastic leukemia | Other: complete blood count<br>* 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.<br>* Other names: bone marrow aspirate;|
| control group<br>healthy age- and sex-matched children without ahistory of any malignancies | Other: complete blood count<br>* 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.<br>* Other names: bone marrow aspirate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FoxO3a and PU.1 levels in acute lymphoblastic leukemia | detection of the mean difference in FoxO3a and PU.1 expression levels between cases and controls | 2 years |