Role of HMOX1 Promoter Genetic Variants in Chemoresistance and Chemotherapy Induced Neutropenia in Children with Acute Lymphoblastic Leukemia
Open Access
- 19 January 2021
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 22 (3), 988
- https://doi.org/10.3390/ijms22030988
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.Funding Information
- Fundacja na rzecz Nauki Polskiej (POMOST/2013-8/2)
- Wydział Lekarski, Uniwersytet Jagielloński Collegium Medicum (: K/DSC/002037)
- Narodowe Centrum Nauki (NCN 2015/18/M/NZ3/00387)
This publication has 110 references indexed in Scilit:
- Murine Bone Marrow Lin−Sca-1+CD45− Very Small Embryonic-Like (VSEL) Cells Are Heterogeneous Population Lacking Oct-4A ExpressionPLOS ONE, 2013
- Malaria impairs resistance to Salmonella through heme- and heme oxygenase–dependent dysfunctional granulocyte mobilizationNature Medicine, 2011
- Effects of heme oxygenase-1 on induction and development of chemically induced squamous cell carcinoma in miceFree Radical Biology & Medicine, 2011
- Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell nicheThe Journal of Experimental Medicine, 2011
- Glucocorticoid use in acute lymphoblastic leukaemiaThe Lancet Oncology, 2010
- Role of Heme Oxygenase-1 in Human Endothelial CellsArteriosclerosis, Thrombosis, and Vascular Biology, 2010
- Hematopoietic stem cell: self‐renewal versus differentiationWires Systems Biology and Medicine, 2010
- Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children's Oncology Group studyLeukemia, 2008
- Heme Oxygenase-1 in Tumors: Is It a False Friend?Antioxidants and Redox Signaling, 2007
- Stromal cell–derived factor 1 promotes angiogenesis via a heme oxygenase 1–dependent mechanismThe Journal of Experimental Medicine, 2007