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Immunophenotyping and Xist Gene in AML (Xist)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04288739
Recruitment Status : Not yet recruiting
First Posted : February 28, 2020
Last Update Posted : July 9, 2020
Information provided by (Responsible Party):
Alaa Mahmoud Ali Kassem, Assiut University

Brief Summary:

Acute myeloid leukemia (AML) is a heterogeneous disorder characterized by clonal expansion of myeloid progenitors (blasts) in the bone marrow and peripheral blood.Several studies have reported correlations of aberrantly expressed markers by flowcytometry with clinical outcome in AML. X-inactive specific transcript RNA was one of the first long noncoding RNAs (lncRNAs) to be discovered in the early 1990s. Xist RNA is the master regulator of XCI, the epigenetic process that equalizes the dosage of X-linked genes between female (XX) and male (XY) mammals. Yildirim et al., (2013) deleted Xist in the blood compartment of mice and demonstrated that mutant females developed a highly aggressive myeloproliferative neoplasm and myelodysplastic syndrome (mixed MPN/MDS) with 100% penetrance.

Their study implies that human hematologic cancers may result from overdosage of X, either from Xist loss on Xi or from duplication of Xa. And they proposed that carcinogenesis is driven by a series of changes occurring in the HSC and further accumulated in mature hematopoietic cells. These changes are initiated by loss of Xist, which leads to progressive X reactivation, which in turn induces a cascade of unfavorable genome-wide changes that include dysregulation of genes involved in DNA replication, chromosome segregation, cell-cycle checkpoints, and hematopoiesis. A failure of HSC maturation and loss of long-term HSC in the marrow progressively shift hematopoiesis to extramedullary sites resulting in extra medullary hematopoiesis (EMH), thereby causally linking the X chromosome to cancer in mice. Thus, they concluded that Xist RNA not only is required to maintain XCI but also suppresses cancer in vivo.

Indeed, the emerging role of aberrant gene dosage in diseases, whether of the X chromosome or for autosomes, brings with it the possible application of drugs that impact on epigenetic regulators in potential therapeutic strategies.

To date, there are no published studies on human about Xist gene and its relationship with the immunophenotyping in AML patients. So, this will be the first study designed to explain its unexplored pathway in AML and detect its prognostic role and immunophenotypic association.

Condition or disease Intervention/treatment
Acute Myeloid Leukemia Diagnostic Test: flow cytometric immunophenotyping Genetic: Xist gene by fluorescence insitu hybridization

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Study Type : Observational
Estimated Enrollment : 65 participants
Observational Model: Case-Only
Time Perspective: Cross-Sectional
Official Title: Relationship Between Immunophenotyping and X-inactive Specific Transcript (Xist) Gene in Acute Myeloid Leukemia
Estimated Study Start Date : October 2, 2020
Estimated Primary Completion Date : May 30, 2022
Estimated Study Completion Date : December 31, 2022

Group/Cohort Intervention/treatment
Acute Myeloid Leukemia (AML) group

patients who are diagnosed as Acute Myeloid Leukemia (AML) based on peripheral blood, bone marrow, immunophenotyping and who fulfill the WHO 2016 criteria.

Complete blood count (CBC), bone marrow aspirate, flow cytometric immunophenotyping, cytogenetic analysis and fluorescence in situ hybridization (FISH) for XIST gene will be performed for all AML patients in the study.

Diagnostic Test: flow cytometric immunophenotyping
Flow cytometric (FCM) immunophenotypic analysis of peripheral blood or bone marrow aspiration samples will be performed using a panel of monoclonal antibodies (HLA DR, CD34, CD117, Cyto MPO, CD13, CD33, CD3, CD4, CD8, CD10, CD19, CD5, CD14, CD64, CD36, CD235a, cyto CD41, cyto CD61).

Genetic: Xist gene by fluorescence insitu hybridization

Fluorescence in situ hybridization (FISH) is a kind of cytogenetic technique that allows the visualization of defined nucleic acid sequences in particular cellular or chromosomal sites by hybridization of complementary fluorescently labeled probe sequences within intact metaphase or interphase cells.

The fluorescent probes are nucleic acid labeled with fluorescent groups and can bind to specific DNA/RNA sequences. Fluorescence microscopy can be used to find out where the fluorescent probe is bound to the chromosomes.

Other Name: FISH

Primary Outcome Measures :
  1. Identify Xist gene by FISH in AML [ Time Frame: 2 years ]
    Identify X- inactive specific transcript (Xist) gene by fluorescence insitu hybridization (FISH) in AML

  2. Integrating multiple strategies ( immunophenotypic fingerprint by flowcytometry and Xist gene by FISH) in AML [ Time Frame: 2 years ]
    Integrating multiple strategies by Identification through multiparametric flow cytometry atdiagnosis of an immunophenotypic fingerprint associated with Xist gene abnormalities, detected by FISH, as a novel and simplified tool with improved sensitivity, to detect these abnormalities may allowing patient stratification and risk adapted treatment with potential impact on outcome of the disease.

Biospecimen Retention:   Samples With DNA
Peripheral blood or bone marrow aspirate samples

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
AML patients, who fulfill the WHO 2016 criteria

Inclusion Criteria:

  • AML patients, who fulfill the WHO 2016 criteria

Exclusion Criteria:

  • patients with other hematological nepolasms (ALL,CLL, plasma cell myeloma)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04288739

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Contact: Alaa M. Kassem, M.Sc +201010328237

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Faculty of medicine
Assiut, Egypt, 71515
Contact: Alaa M. Kassem, M.Sc    +201010328237   
Sponsors and Collaborators
Assiut University
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Study Director: Shaaban R. Helal, MD faculty of medicine

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Responsible Party: Alaa Mahmoud Ali Kassem, Assistant lecturer, Assiut University Identifier: NCT04288739    
Other Study ID Numbers: AssiutU-CP-Xist 90
First Posted: February 28, 2020    Key Record Dates
Last Update Posted: July 9, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alaa Mahmoud Ali Kassem, Assiut University:
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type