FoxO3a and PU.1 in Acute Lymphoblastic Leukemia

NCT ID: NCT04092348

Last Updated: 2023-02-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Total Enrollment

53 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-08-01

Study Completion Date

2024-12-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Acute Lymphoblastic Leukemia

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

OTHER

Study Time Perspective

CROSS_SECTIONAL

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

study group

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

complete blood count

Intervention Type OTHER

1. total RNA is isolated from fresh blood samples
2. RNA is converted into complementary DNA c.DNA
3. 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.

control group

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

complete blood count

Intervention Type OTHER

1. total RNA is isolated from fresh blood samples
2. RNA is converted into complementary DNA c.DNA
3. 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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

complete blood count

1. total RNA is isolated from fresh blood samples
2. RNA is converted into complementary DNA c.DNA
3. 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.

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

bone marrow aspirate

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

2 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Assiut University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

MRA Youb

principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Rania Mohamed Bakry, Professor

Role: CONTACT

01221031572

Dina Ismail El kady, Lecturer

Role: CONTACT

01118707090

References

Explore related publications, articles, or registry entries linked to this study.

Ferber EC, Peck B, Delpuech O, Bell GP, East P, Schulze A. FOXO3a regulates reactive oxygen metabolism by inhibiting mitochondrial gene expression. Cell Death Differ. 2012 Jun;19(6):968-79. doi: 10.1038/cdd.2011.179. Epub 2011 Dec 2.

Reference Type BACKGROUND
PMID: 22139133 (View on PubMed)

Inaba H, Greaves M, Mullighan CG. Acute lymphoblastic leukaemia. Lancet. 2013 Jun 1;381(9881):1943-55. doi: 10.1016/S0140-6736(12)62187-4. Epub 2013 Mar 22.

Reference Type BACKGROUND
PMID: 23523389 (View on PubMed)

Kerdiles YM, Beisner DR, Tinoco R, Dejean AS, Castrillon DH, DePinho RA, Hedrick SM. Foxo1 links homing and survival of naive T cells by regulating L-selectin, CCR7 and interleukin 7 receptor. Nat Immunol. 2009 Feb;10(2):176-84. doi: 10.1038/ni.1689. Epub 2009 Jan 11.

Reference Type BACKGROUND
PMID: 19136962 (View on PubMed)

Pui CH. Acute lymphoblastic leukemia: introduction. Semin Hematol. 2009 Jan;46(1):1-2. doi: 10.1053/j.seminhematol.2008.09.011. No abstract available.

Reference Type BACKGROUND
PMID: 19100362 (View on PubMed)

Xie Y, Davies SM, Xiang Y, Robison LL, Ross JA. Trends in leukemia incidence and survival in the United States (1973-1998). Cancer. 2003 May 1;97(9):2229-35. doi: 10.1002/cncr.11316.

Reference Type BACKGROUND
PMID: 12712476 (View on PubMed)

Yang XB, Zhao JJ, Huang CY, Wang QJ, Pan K, Wang DD, Pan QZ, Jiang SS, Lv L, Gao X, Chen HW, Yao JY, Zhi M, Xia JC. Decreased expression of the FOXO3a gene is associated with poor prognosis in primary gastric adenocarcinoma patients. PLoS One. 2013 Oct 23;8(10):e78158. doi: 10.1371/journal.pone.0078158. eCollection 2013.

Reference Type BACKGROUND
PMID: 24194912 (View on PubMed)

Zhang X, Tang N, Hadden TJ, Rishi AK. Akt, FoxO and regulation of apoptosis. Biochim Biophys Acta. 2011 Nov;1813(11):1978-86. doi: 10.1016/j.bbamcr.2011.03.010. Epub 2011 Mar 31.

Reference Type BACKGROUND
PMID: 21440011 (View on PubMed)

Ausserlechner MJ, Salvador C, Deutschmann A, Bodner M, Viola G, Bortolozzi R, Basso G, Hagenbuchner J, Obexer P. Therapy-resistant acute lymphoblastic leukemia (ALL) cells inactivate FOXO3 to escape apoptosis induction by TRAIL and Noxa. Oncotarget. 2013 Jul;4(7):995-1007. doi: 10.18632/oncotarget.953.

Reference Type RESULT
PMID: 23828551 (View on PubMed)

Chiaretti S, Zini G, Bassan R. Diagnosis and subclassification of acute lymphoblastic leukemia. Mediterr J Hematol Infect Dis. 2014 Nov 1;6(1):e2014073. doi: 10.4084/MJHID.2014.073. eCollection 2014.

Reference Type RESULT
PMID: 25408859 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

madonna

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.