Title:New Candidate Genes for Lack of Sensitivity to Therapy in Pediatric Leukemias
Volume: 17
Issue: 4
Author(s): Weronika Bereza, Joanna Szczepanek*, Joanna Laskowska and Andrzej Tretyn
Affiliation:
- Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, Wilenska 4, 87- 100 Torun,Poland
Keywords:
Quantative trait loci (QTL), multidrug resistance, genome-wide association studies (GWAS), linkage mapping approach,
genetic profiling, biomarkers.
Abstract: In the recent years, significant development of molecular genetics has contributed to the
better understanding of leukemogenesis and classification of the different leukemia subtypes. Patients
diagnosed with acute leukemia usually undergo chemotherapy, which involves the induction of remission,
consolidation of remission and maintenance therapy. Patients are still vulnerable to relapse due to
differences in the sensitivity of leukemia cells to the chemotherapeutic agent, because of the active
drugs removal from the cells, improving the repair of DNA damage or abnormalities in the apoptotic
pathway. Cell adhesion and miRNA expression level also affect the drug resistance. New candidate
genes and genes correlated with the disease have been sought to increase the survival of patients with
leukemia. Candidate gene is usually a loci located in a certain chromosomal region suspected of involvement
to the disease course or its expression product regulates disease progression. There are classic
and digital methods of finding candidate genes. These techniques are inexpensive, quick and easy to
carry out. Unfortunately, due to insufficient knowledge of the disease etiology and low accuracy, researchers
cannot detect all genes, involved in leukemogenesis and cell resistance. Currently, scientists
have many tools used for selecting genes, such as expression microarrays, comparative genomic hybridization
and next generation sequencing. Among the validation techniques for candidate genes, the
mostly used ones are fluorescent in situ hybridization and real-time PCR. In our review we present 18
candidate genes of resistance to therapy in childhood leukemia.
