Role of HMOX1 Promoter Genetic Variants in Chemoresistance and Chemotherapy Induced Neutropenia in Children with Acute Lymphoblastic Leukemia |
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| Authors: | Karolina Bukowska-Strakova Joanna W&#x;odek Ewelina Pitera Magdalena Kozakowska Anna Konturek-Cie la Maciej Cie la Monika Go&#x;ka Witold Nowak Aleksandra Wieczorek Katarzyna Pawi&#x;ska-W&#x;sikowska Alicja Jzkowicz Maciej Siedlar |
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| Affiliation: | 1.Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, 31-663 Kraków, Poland; (J.W.); (E.P.);2.Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 31-007 Kraków, Poland; (M.K.); (A.K.-C.); (M.C.); (M.G.); (W.N.);3.Pediatric, Oncology and Hematology Department, Institute of Pediatrics, Jagiellonian University Medical College, 30-387 Krakow, Poland; (A.W.); (K.P.-W.) |
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| Abstract: | 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(−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. |
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| Keywords: | pediatric acute lymphoblastic leukemia heme oxygenase-1 chemotherapy induced neutropenia minimal residual disease |
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