Effects of Reduced Mir-24 Expression on Plasma Methotrexate Levels, Therapy-Related Toxicities, and Patient Outcomes in Pediatric Acute Lymphoblastic Leukemia.

Acute Lymphoblastic Leukemia Event Free Survival Methotrexate Mir Toxicity

Journal

Reports of biochemistry & molecular biology
ISSN: 2322-3480
Titre abrégé: Rep Biochem Mol Biol
Pays: Iran
ID NLM: 101637937

Informations de publication

Date de publication:
Jan 2020
Historique:
entrez: 26 6 2020
pubmed: 26 6 2020
medline: 26 6 2020
Statut: ppublish

Résumé

The current study aims to investigate the relationship of miR-24 expression with plasma methotrexate (MTX) levels, therapy-related toxicities, and event-free survival (EFS) in Iranian pediatric acute lymphoblastic leukemia (ALL) patients. The study included 74 ALL patients in consolidation phase and 41 healthy children. RNA was extracted from plasma, polyadenylated, and reverse transcribed. miR-24 expression was determined by quantitative polymerase chain reaction (qPCR). Plasma MTX concentrations were measured by high performance liquid chromatography (HPLC) 48 h after high-dose methotrexate (HD-MTX) injection. The diagnosis of ALL was further subclassified as B-ALL or T-ALL via flow cytometry. miR-24 expression was less in pediatric ALL patients than in the control group (p = 0.0038). Furthermore, downregulation of miR-24 was correlated with intermediate- to high-grade HD-MTX therapy toxicities (p = 0.025). Nevertheless, no statistically significant associations were seen between miR-24 levels and plasma MTX levels 48 h after HD-MTX administration (p > 0.05) or EFS in pediatric ALL patients (p > 0.05). miR-24 expression may contribute to interindividual variability in response to intermediate- to highgrade HD-MTX therapy toxicities under Berlin Frankfurt Munster (BFM) treatment.

Sections du résumé

BACKGROUND BACKGROUND
The current study aims to investigate the relationship of miR-24 expression with plasma methotrexate (MTX) levels, therapy-related toxicities, and event-free survival (EFS) in Iranian pediatric acute lymphoblastic leukemia (ALL) patients.
METHODS METHODS
The study included 74 ALL patients in consolidation phase and 41 healthy children. RNA was extracted from plasma, polyadenylated, and reverse transcribed. miR-24 expression was determined by quantitative polymerase chain reaction (qPCR). Plasma MTX concentrations were measured by high performance liquid chromatography (HPLC) 48 h after high-dose methotrexate (HD-MTX) injection. The diagnosis of ALL was further subclassified as B-ALL or T-ALL via flow cytometry.
RESULTS RESULTS
miR-24 expression was less in pediatric ALL patients than in the control group (p = 0.0038). Furthermore, downregulation of miR-24 was correlated with intermediate- to high-grade HD-MTX therapy toxicities (p = 0.025). Nevertheless, no statistically significant associations were seen between miR-24 levels and plasma MTX levels 48 h after HD-MTX administration (p > 0.05) or EFS in pediatric ALL patients (p > 0.05).
CONCLUSION CONCLUSIONS
miR-24 expression may contribute to interindividual variability in response to intermediate- to highgrade HD-MTX therapy toxicities under Berlin Frankfurt Munster (BFM) treatment.

Identifiants

pubmed: 32582793
pii: rbmb-8-358
pmc: PMC7275838

Types de publication

Journal Article

Langues

eng

Pagination

358-365

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Auteurs

Mohammad Ali Esmaili (MA)

Department of Hematology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran .

Ahmad Kazemi (A)

Department of Hematology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran .

Farhad Zaker (F)

Department of Hematology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran .

Mohammad Faranoush (M)

Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran .
Mahak Hematology Oncology Research Center (MAHAK-HORC), Mahak Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Mohammad Reza Rezvany (MR)

Department of Hematology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran .
Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran .
Department of Oncology-Pathology, Immune and Gene Therapy Lab, Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institute, Stockholm 17176, Sweden.

Classifications MeSH