Analysis of expression of MSH2 and MSH3 genes in MLL-Acute Lymphoblastic Leukemia (ALL) human cell lines

Kulsom Nuuri, Yoana Arroyo, Maria Esposito

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Abstract

Around 820 new cases of Acute Lymphoblastic Leukemia (ALL) are diagnosed in the United Kingdom every year. Cytarabine (Ara-C) is a chemotherapeutic drug used to treat leukemic patients, however, chemotherapy resistance occurs frequently. Mechanisms of chemotherapy resistance to Ara-C are poorly understood. DNA mismatch repair (MMR) pathway is one of the pathways responsible to repair errors caused during DNA replication. MMR can also repair the damage due to Ara-C and therefore a proficient MMR can confer resistance to Ara-C. Our project aims to investigate the expression of MMR genes MSH2 and MSH3 in ALL carrying MLL (Mixed Lineage Leukemia, also known as KMT2A) chromosomal translocations. The purpose of this study was to examine a potential correlation between the expression of these genes in MLL-ALL and Ara-C resistance. RNA was isolated from cultured cell lines: Kasumi-1 and K562 (positive non MLL controls) and HB-1119 and SEM-1 (experimental MLL-cell lines), retro-transcribed into cDNA. Endpoint and Semi-quantitative PCR were employed to amplify the cDNA and analyze the expression of MSH2 and MSH3 in the experimental cell lines. The results indicate that MSH2 and MSH3 are expressed in both Ara-C resistant MLL-ALL cell lines HB-1119 and SEM-1 and that the expression levels in HB-1119 were lower than SEM1. Further research is needed to understand the contribution of MMR to Ara-C response in ALL. This research should be focused on testing the functionality of MMR in Ara-C resistant and sensitive leukemic cell lines. Furthermore, the contribution of each MMR genes to Ara-C resistance should be addressed by knock-down and over-expression studies.

© 2020 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0/
Original languageEnglish
JournalJournal of Young Investigator
Publication statusPublished - 1 Apr 2020

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