Role of HMOX1 Promoter Genetic Variants in Chemoresistance and Chemotherapy Induced Neutropenia in Children with Acute Lymphoblastic Leukemia
| Autor: | Aleksandra Wieczorek, Maciej Cieśla, Witold Nowak, Monika Gońka, Anna Konturek-Cieśla, Katarzyna Pawińska-Wąsikowska, Ewelina Pitera, Alicja Jozkowicz, Karolina Bukowska-Strakova, Magdalena Kozakowska, Joanna Włodek, Maciej Siedlar |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Single-nucleotide polymorphism
Neutropenia Biology Catalysis pediatric acute lymphoblastic leukemia Inorganic Chemistry lcsh:Chemistry Polymorphism (computer science) medicine SNP Physical and Theoretical Chemistry Allele Molecular Biology Gene Childhood Acute Lymphoblastic Leukemia lcsh:QH301-705.5 Spectroscopy Organic Chemistry heme oxygenase-1 General Medicine medicine.disease Minimal residual disease Computer Science Applications lcsh:Biology (General) lcsh:QD1-999 Cancer research minimal residual disease chemotherapy induced neutropenia |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 3 International Journal of Molecular Sciences, Vol 22, Iss 988, p 988 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22030988 |
| Popis: | Whilst the survival rates of childhood acute lymphoblastic leukemia (ALL) have increased remarkably over the last decades, the therapy resistance and toxicity are still the major causes of treatment failure. It was shown that overexpression of heme oxygenase-1 (HO-1) promotes proliferation and chemoresistance of cancer cells. In humans, the HO-1 gene (HMOX1) expression is modulated by two polymorphisms in the promoter region: (GT)n-length polymorphism and single-nucleotide polymorphism (SNP) A(&minus 413)T, with short GT repeat sequences and 413-A variants linked to an increased HO-1 inducibility. We found that the short alleles are significantly more frequent in ALL patients in comparison to the control group, and that their presence may be associated with a higher risk of treatment failure, reflecting the role of HO-1 in chemoresistance. We also observed that the presence of short alleles may predispose to develop chemotherapy-induced neutropenia. In case of SNP, the 413-T variant co-segregated with short or long alleles, while 413-A almost selectively co-segregated with long alleles, hence it is not possible to determine if SNPs are actually of phenotypic significance. Our results suggest that HO-1 can be a potential target to overcome the treatment failure in ALL patients. |
| Databáze: | OpenAIRE |
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