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CIRCULATING MICRORNA MIR-99B AND MIR-125A IN MYELODYSPLASTIC SYNDROME-NONINVASIVE DIAGNOSTIC AND PROGNOSTIC BIOMARKERS
Author(s): ,
Inga Mandac Smoljanovic
Affiliations:
Clinical Hospital Merkur,Zagreb,Croatia
,
Mirjana Mariana Kardum Paro
Affiliations:
Clinical Hospital Merkur,Zagreb,Croatia
,
Milunovic Vibor
Affiliations:
Clinical Hospital Merkur,Zagreb,Croatia
,
Delfa Radic Kristo
Affiliations:
Clinical Hospital Merkur,Zagreb,Croatia
,
Milan Milosevic
Affiliations:
School of Medicine,Zagreb,Croatia
Slobodanka Ostojic Kolonic
Affiliations:
Clinical Hospital Merkur,Zagreb,Croatia
EHA Library. MANDAC ROGULJ I. 06/09/21; 325690; EP932
Inga MANDAC ROGULJ
Inga MANDAC ROGULJ
Contributions
Abstract
Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP932

Type: E-Poster Presentation

Session title: Myelodysplastic syndromes - Clinical

Background

Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal hematologic disorders of hematopoietic stem cells, followed by ineffective hematopoiesis of one or more cell lines with the onset of consequent cytopenia with an increased risk of progression to acute myeloid leukemia. According to the World Health Organization classification, the diagnosis of MDS is based on morphological, clinical, cytogenetic, immunophenotypic and biological criteria.


In everyday clinical practice, the diagnosis of MDS is based on invasive cytomorphological analysis of peripheral blood and bone marrow cells, determination of blast percent, type and degree of dysplasia, presence of ring sideroblasts, and cytogenetic analysis of bone marrow cells.


Micro Messenger Ribonucleic Acids (miRNAs) are short, non-coding molecules of 18 to 25 nucleotides in length that play an important role in regulating cell development and metabolism, their differentiation and proliferation, regulation of the cell cycle and cell death. Tumor cells release miRNAs into the circulation (plasma, serum) where they remain relatively stable. Although their discovery allowed linking of disease and miRNA gene expression, a precondition for their clinical application was the determination of gene expression by real-time quantitative polymerase chain reaction with satisfactory efficacy and specificity. In the literature, gene expression of miRNAs has been linked to the diagnosis, classification and progression of various diseases.


Many studies have been conducted so far about the molecular mechanisms and epigenetic pathways in MDS and their prognostic and therapeutic significance, but few studies have analyzed the importance of miRNAs in MDS.

Aims

The aim of this study was to examine the level of change of gene expression of specific mRNAs (miR-125a, miR-99b, miR-126, miR-125b, miR-let-7a) in plasma of healthy volunteers and subjects diagnosed with MDS.

Methods

Gene expressions of miRNAs were determined at the Clinical Institute of Medical Biochemistry and Laboratory Medicine, Merkur University Hospital, accredited according to EN ISO 15189:2012, in plasma samples of 20 healthy volunteers and 41 MDS patients diagnosed at the Institute of Hematology of the Clinic for Internal Diseases of Merkur University Hospital, Reference Center of the Ministry of Health of the Republic of Croatia for Diagnosis and Treatment of MDS. 

Results

A significant difference was found between the study group and healthy control in miR-99b level, where at normalized values relative to miR-126, an increased level in subjects compared to control was observed 4,521 times (P = 0.004).


There was negative correlation between miR-125a(rho=-0,326; P=0,038), RBC count and hemoglobin level (rho=-0,381; P=0,014).


miR-99b showed statistically significant positive correlation with WBC count (rho=0,310; P=0,048). 

Conclusion
MiR-99b and 125a could serve as diagnostic and prognostic noninvasive biomarkers in MDS.

The results of the study suggest that gene expression of miRs (125a, 125b, 99b, let7a) could be regulated by the same mechanism and may be clinically relevant in subjects with MDS.

Keyword(s): Diagnosis, MDS, Prognostic factor

Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP932

Type: E-Poster Presentation

Session title: Myelodysplastic syndromes - Clinical

Background

Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal hematologic disorders of hematopoietic stem cells, followed by ineffective hematopoiesis of one or more cell lines with the onset of consequent cytopenia with an increased risk of progression to acute myeloid leukemia. According to the World Health Organization classification, the diagnosis of MDS is based on morphological, clinical, cytogenetic, immunophenotypic and biological criteria.


In everyday clinical practice, the diagnosis of MDS is based on invasive cytomorphological analysis of peripheral blood and bone marrow cells, determination of blast percent, type and degree of dysplasia, presence of ring sideroblasts, and cytogenetic analysis of bone marrow cells.


Micro Messenger Ribonucleic Acids (miRNAs) are short, non-coding molecules of 18 to 25 nucleotides in length that play an important role in regulating cell development and metabolism, their differentiation and proliferation, regulation of the cell cycle and cell death. Tumor cells release miRNAs into the circulation (plasma, serum) where they remain relatively stable. Although their discovery allowed linking of disease and miRNA gene expression, a precondition for their clinical application was the determination of gene expression by real-time quantitative polymerase chain reaction with satisfactory efficacy and specificity. In the literature, gene expression of miRNAs has been linked to the diagnosis, classification and progression of various diseases.


Many studies have been conducted so far about the molecular mechanisms and epigenetic pathways in MDS and their prognostic and therapeutic significance, but few studies have analyzed the importance of miRNAs in MDS.

Aims

The aim of this study was to examine the level of change of gene expression of specific mRNAs (miR-125a, miR-99b, miR-126, miR-125b, miR-let-7a) in plasma of healthy volunteers and subjects diagnosed with MDS.

Methods

Gene expressions of miRNAs were determined at the Clinical Institute of Medical Biochemistry and Laboratory Medicine, Merkur University Hospital, accredited according to EN ISO 15189:2012, in plasma samples of 20 healthy volunteers and 41 MDS patients diagnosed at the Institute of Hematology of the Clinic for Internal Diseases of Merkur University Hospital, Reference Center of the Ministry of Health of the Republic of Croatia for Diagnosis and Treatment of MDS. 

Results

A significant difference was found between the study group and healthy control in miR-99b level, where at normalized values relative to miR-126, an increased level in subjects compared to control was observed 4,521 times (P = 0.004).


There was negative correlation between miR-125a(rho=-0,326; P=0,038), RBC count and hemoglobin level (rho=-0,381; P=0,014).


miR-99b showed statistically significant positive correlation with WBC count (rho=0,310; P=0,048). 

Conclusion
MiR-99b and 125a could serve as diagnostic and prognostic noninvasive biomarkers in MDS.

The results of the study suggest that gene expression of miRs (125a, 125b, 99b, let7a) could be regulated by the same mechanism and may be clinically relevant in subjects with MDS.

Keyword(s): Diagnosis, MDS, Prognostic factor

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