Acute Lymphoblastic LeukemiaNCT04092348
FoxO3a and PU.1 in Acute Lymphoblastic Leukemia
An observational study of Acute Lymphoblastic Leukemia, run by Assiut University.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia
- What is being tested?
- complete blood count
- How many people
- 53 participants
- Where
- No sites listed yet
- Study dates
- 1 Aug 2023to 30 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Study population: * cases 1. inclusion criteria: children aged 2-17 years and diagnosed as new cases of acute lymphoblastic leukemia 2. 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 * controls (healthy age- and sex-matched children without ahistory of any malignancies)
Who may be able to join
- children aged 2-17 years and diagnosed as new cases of acute lymphoblastic leukemia
Who cannot join
- age more than 17 years
- presence of other hematological disorders, history of other malignancies ,or relapsed ALL
- patients under chemotherapy or radiotherapy
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Value of FoxO3a and PU.1 Expression in Pediatric Acute Lymphoblastic Leukemia
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.
Read the 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.
- Conditions
- Acute Lymphoblastic Leukemia
- Being tested
- complete blood count
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
complete blood countOther
Also called bone marrow aspirate
- 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.
| Study group | Role | What they receive |
|---|---|---|
| study group | children aged 2-17 years and diagnosed as new cases of acute lymphoblastic leukemia Receives: Other: complete blood count | |
| control group | healthy age- and sex-matched children without ahistory of any malignancies Receives: Other: complete blood count |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2019
- Study start1 Aug 2023 (estimated)
- Primary completion30 Mar 2024 (estimated)
- Study completion30 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 53 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, MRA Youb, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04092348
- Sponsor's protocol ID
- madonna
- Status last verified
- Feb 2023
- First submitted
- 14 Sep 2019
- Last updated
- 8 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 22139133Inaba 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.
PubMed 23523389Kerdiles 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.
PubMed 19136962Pui CH. Acute lymphoblastic leukemia: introduction. Semin Hematol. 2009 Jan;46(1):1-2. doi: 10.1053/j.seminhematol.2008.09.011. No abstract available.
PubMed 19100362Xie 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.
PubMed 12712476Yang 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.
PubMed 24194912Zhang 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.
PubMed 21440011Ausserlechner 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.
PubMed 23828551Chiaretti 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.
PubMed 25408859
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Value of FoxO3a and PU.1 Expression in Pediatric Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT04092348
- Acronym / sponsor ID
- madonna
- Conditions
- Acute Lymphoblastic Leukemia
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 53 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Aug 2023 (estimated)
- Primary completion
- 30 Mar 2024 (estimated)
- Study completion
- 30 Dec 2024 (estimated)
- First posted
- 17 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Other
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| study group | – | Other: complete blood countchildren aged 2-17 years and diagnosed as new cases of acute lymphoblastic leukemia |
| control group | – | Other: complete blood counthealthy age- and sex-matched children without ahistory of any malignancies |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- * cases 1. inclusion criteria: children aged 2-17 years and diagnosed as new cases of acute lymphoblastic leukemia 2. 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 * controls (healthy age- and sex-matched children without ahistory of any malignancies)
Key inclusion criteria (1 listed)
- children aged 2-17 years and diagnosed as new cases of acute lymphoblastic leukemia
Key exclusion criteria (3 listed)
- age more than 17 years
- presence of other hematological disorders, history of other malignancies ,or relapsed ALL
- patients under chemotherapy or radiotherapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| complete blood countAlso: bone marrow aspirate1. 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. | Other | control group, study group |
Primary outcome
FoxO3a and PU.1 levels in acute lymphoblastic leukemia
Time frame: 2 years
detection of the mean difference in FoxO3a and PU.1 expression levels between cases and controls
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
- Background: PubMed 22139133Ferber 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.
- Background: PubMed 23523389Inaba 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.
- Background: PubMed 19136962Kerdiles 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.
- Background: PubMed 19100362Pui CH. Acute lymphoblastic leukemia: introduction. Semin Hematol. 2009 Jan;46(1):1-2. doi: 10.1053/j.seminhematol.2008.09.011. No abstract available.
- Background: PubMed 12712476Xie 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.
- Background: PubMed 24194912Yang 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.
- Background: PubMed 21440011Zhang 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.
- Results publication: PubMed 23828551Ausserlechner 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.
- Results publication: PubMed 25408859Chiaretti 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Lymphoblastic Leukemia, run by Assiut University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rania Mohamed Bakry, Professor (01221031572, Rbakry.md@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
FoxO3a and PU.1 levels in acute lymphoblastic leukemia (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04092348, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2023.