NCT04288739: Xist

Immunophenotyping and Xist Gene in AML

Status unknown Last updated 9 July 2020

What this trial tests

trial testing flow cytometric immunophenotyping in Acute Myeloid Leukemia in 65 participants. Status unknown.

Timeline

2 October 2020

Primary endpoint
30 May 2022

31 December 2022

Quick facts

Lead sponsor	Assiut University
Status	Status unknown
Study type	OBSERVATIONAL
Enrollment	65
Start date	2 October 2020
Primary completion	30 May 2022
Estimated completion	31 December 2022
Sites	1 location across Egypt

Drugs / interventions tested

• flow cytometric immunophenotyping
• Xist gene by fluorescence insitu hybridization

Conditions studied

• Acute Myeloid Leukemia — all drugs for Acute Myeloid Leukemia →

Sponsor

Assiut University

Who can join

Eligibility, any sex, with Acute Myeloid Leukemia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Mechanisms of Long Non-Coding RNAs in Cancers and Their Dynamic Regulations.
   Zhang XZ, Liu H, Chen SR. · · 2020 · cited 109× · PMID 32429086 · DOI 10.3390/cancers12051245
2. Non-coding RNAs and epithelial mesenchymal transition in cancer: molecular mechanisms and clinical implications.
   Khanbabaei H, Ebrahimi S, García-Rodríguez JL, Ghasemi Z, et al · · 2022 · cited 36× · PMID 36114510 · DOI 10.1186/s13046-022-02488-x
3. Non-coding RNAs as therapeutic targets in cancer and its clinical application.
   Leng X, Zhang M, Xu Y, Wang J, et al · · 2024 · cited 20× · PMID 39149142 · DOI 10.1016/j.jpha.2024.02.001
4. Hidden Treasures: Macrophage Long Non-Coding RNAs in Lung Cancer Progression.
   Karger A, Nandigama R, Stenzinger A, Grimminger F, et al · · 2021 · cited 11× · PMID 34439281 · DOI 10.3390/cancers13164127
5. Competitive Endogenous RNA Network Involving miRNA and lncRNA in Non-Hodgkin Lymphoma: Current Advances and Clinical Perspectives.
   Fernandes M, Marques H, Teixeira AL, Medeiros R. · · 2021 · cited 3× · PMID 34944752 · DOI 10.3390/biomedicines9121934