HMGB1 Polymorphisms in Acute Lymphoblastic Leukemia
-
Elham Rayzan
,
Saeed Farajzadeh Valilou
,
Sara Hemmati
,
Amin Sadeghi
,
Hamid Farajifard
,
Sepideh Shahkarami
,
Nima Rezaei
Abstract
Background: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and the leading cause of childhood death in contrast to the 90% cure rate. ALL includes different subtypes described by interrupt collections of somatic chromosomal alterations and sequence mutations that disrupt normal body functions such as lymphoid maturation, cell-cycle regulation, and tumor suppression. Having a significant role in several cancers, the high mobility group box-1 (HMGB1) gene is considered an important gene in the development of tumors.
Methods: Herein, the genetic role of HMGB1 was studied in the 49 Iranian patients with newly diagnosed ALL using Sanger sequencing of HMGB1 coding regions (exons 2 to 5).
Results: The results showed that none of the subjects in the study had any promising variants in the coding sequences of the HMGB1.
Conclusion: These findings suggest that HMGB1 is not directly associated with ALL incidence and behavior. Further investigations using a large group of patients with different races and ethnicities are required to analyze the possible role of HMGB1 gene polymorphisms in ALL patients.
1. Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med. 2015;373(16):1541-52.
2. Iacobucci I, Mullighan CG. Genetic basis of acute lymphoblastic leukemia. J Clin Oncol. 2017;35(9):975.
3. Mullighan CG, Su X, Zhang J, Ma J, Radtke I, Phillips LA, et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med. 2009;360(5):470-80.
4. Churchman ML, Qian M, Te Kronnie G, Zhang R, Yang W, Schewe DM, et al. Germline genetic IKZF1 variation and predisposition to childhood acute lymphoblastic leukemia. Cancer Cell. 2018;33(5):937-48.e8.
5. Hein D, Borkhardt A, Fischer U. Insights into the prenatal origin of childhood acute lymphoblastic leukemia. Cancer Metastasis Rev. 2020;1-11.
6. Yang H, Wang H, Czura CJ, Tracey KJ. HMGB1 as a cytokine and therapeutic target. J Endotoxin Res. 2002;8(6):469-72.
7. Chen G, Ward MF, Sama AE, Wang H. Extracellular HMGB1 as a proinflammatory cytokine. J Interferon Cytokine Res. 2004;24(6):329-33.
8. Thomas JO, Travers AA. HMG1 and 2, and related ‘architectural’ DNA-binding proteins. Trends Biochem Sci. 2001;26(3):167-74.
9. Kang R, Chen R, Zhang Q, Hou W, Wu S, Cao L, et al. HMGB1 in health and disease. Mol Aspects Med. 2014;40:1-116.
10. Tang D, Billiar TR, Lotze MT. A Janus tale of two active high mobility group box 1 (HMGB1) redox states. Mol Med. 2012;18(10):1360-2.
11. Klune JR, Dhupar R, Cardinal J, Billiar TR, Tsung A. HMGB1: endogenous danger signaling. Mol Med. 2008;14(7-8):476-84.
12. Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ. HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol. 2009;28:367-88.
13. Aychek T, Miller K, Sagi-Assif O, Schori C, Salmon-Divon M, Witz IP, et al. E-selectin regulates gene expression in metastatic colorectal carcinoma cells and enhances HMGB1 release. Int J Cancer. 2008;123(8):1741-50.
14. Andersson U, Wang H, Palmblad K, Aveberger AC, Bloom O, Erlandsson-Harris H, et al. High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med. 2000;192(4):565-70.
15. Brunetti A, Manfioletti G, Chiefari E, Goldfine ID, Foti D. Transcriptional regulation of human insulin receptor gene by the high-mobility group protein HMGI(Y). FASEB J. 2001;15(2):492-500.
16. Baldassarre G, Battista S, Belletti B, Pierantoni GM, Fusco A, Thakur S, et al. Negative regulation of BRCA1 gene expression by HMGA1 proteins accounts for the reduced BRCA1 protein levels in sporadic breast carcinoma. Mol Cell Biol. 2003;23(7):2225-38.
17. Dong XDE, Ito N, Lotze MT, DeMarco RA, Popovic P, Shand SH, et al. High mobility group box I (HMGB1) release from tumor cells after treatment: implications for development of targeted chemoimmunotherapy. J Immunother. 2007;30(6):596-606.
18. Dolde CE, Mukherjee M, Cho C, Resar LM. HMG-I/Y in human breast cancer cell lines. Breast Cancer Res Treat. 2002;71(3):181-91.
19. Fedele M, Bandiera A, Chiappetta G, Battista S, Viglietto G, Manfioletti G, et al. Human colorectal carcinomas express high levels of high mobility group HMGI(Y) proteins. Cancer Res. 1996;56(8):1896-901.
20. Tarbé N, Evtimova V, Burtscher H, Jarsch M, Alves F, Weidle UH, et al. Transcriptional profiling of cell lines derived from an orthotopic pancreatic tumor model reveals metastasis-associated genes. Anticancer Res. 2001;21(5):3221-8.
21. Leman ES, Madigan MC, Brünagel G, Takaha N, Coffey DS, Getzenberg RH, et al. Nuclear matrix localization of high mobility group protein I(Y) in a transgenic mouse model for prostate cancer. J Cell Biochem. 2003;88(3):599-608.
22. Petit A, Ragu C, Della-Valle V, Bernard OA, Fenaux P, Mozziconacci MJ, et al. NUP98–HMGB3: a novel oncogenic fusion. Leukemia. 2010;24(3):654-8.
23. Passalacqua M, Zicca A, Sparatore B, Patrone M, Melloni E, Pontremoli S, et al. Secretion and binding of HMG1 protein to the external surface of the membrane are required for murine erythroleukemia cell differentiation. FEBS Lett. 1997;400(3):275-9.
24. Zhu H, Wang L, Ruan Y, Zhang Y, Chen W, Xie M, et al. An efficient delivery of DAMPs on the cell surface by the unconventional secretion pathway. Biochem Biophys Res Commun. 2011;404(3):790-5.
25. Hanspal M, Hanspal JS. The association of erythroblasts with macrophages promotes erythroid proliferation and maturation: a 30-kD heparin-binding protein is involved in this contact. Blood. 1994.
26. Maugeri N, Franchini S, Campana L, Baldini M, Ramirez GA, Sabbadini MG, et al. Circulating platelets as a source of the damage-associated molecular pattern HMGB1 in patients with systemic sclerosis. Autoimmunity. 2012;45(8):584-7.
27. Mitroulis I, Kambas K, Chrysanthopoulou A, Skendros P, Mitroulis SA, Ritis K, et al. Neutrophil extracellular trap formation is associated with IL-1β and autophagy-related signaling in gout. PLoS One. 2011;6(12):e29318.
28. Tadie J-M, Bae H-B, Jiang S, Park DW, Bell CP, Yang H, et al. HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4. Am J Physiol Lung Cell Mol Physiol. 2013;304(5):L342-9.
29. Jia L, Clear A, Liu F-T, Li K, Spence P, Ramsay A, et al. Extracellular HMGB1 promotes differentiation of nurse-like cells in chronic lymphocytic leukemia. Blood. 2014;123(11):1709-19.
30. Aneja RK, Tsung A, Sjodin H, Klune JR, Shin JH, Kaczorowski DJ, et al. Preconditioning with high mobility group box 1 (HMGB1) induces lipopolysaccharide (LPS) tolerance. J Leukoc Biol. 2008;84(5):1326-34.
31. Dahlhaus M, Schult C, Lange S, Freund M, Junghanss C, Junghanss C, et al. MicroRNA 181a influences the expression of HMGB1 and CD4 in acute leukemias. Anticancer Res. 2013;33(2):445-52.
32. Kang R, Tang D, Cao L, Yu Y, Zhang G, Xiao X, et al. High mobility group box 1 is increased in children with acute lymphocytic leukemia and stimulates the release of tumor necrosis factor-alpha in leukemic cells. Zhonghua Er Ke Za Zhi. 2007;45(5):329-33.
2. Iacobucci I, Mullighan CG. Genetic basis of acute lymphoblastic leukemia. J Clin Oncol. 2017;35(9):975.
3. Mullighan CG, Su X, Zhang J, Ma J, Radtke I, Phillips LA, et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med. 2009;360(5):470-80.
4. Churchman ML, Qian M, Te Kronnie G, Zhang R, Yang W, Schewe DM, et al. Germline genetic IKZF1 variation and predisposition to childhood acute lymphoblastic leukemia. Cancer Cell. 2018;33(5):937-48.e8.
5. Hein D, Borkhardt A, Fischer U. Insights into the prenatal origin of childhood acute lymphoblastic leukemia. Cancer Metastasis Rev. 2020;1-11.
6. Yang H, Wang H, Czura CJ, Tracey KJ. HMGB1 as a cytokine and therapeutic target. J Endotoxin Res. 2002;8(6):469-72.
7. Chen G, Ward MF, Sama AE, Wang H. Extracellular HMGB1 as a proinflammatory cytokine. J Interferon Cytokine Res. 2004;24(6):329-33.
8. Thomas JO, Travers AA. HMG1 and 2, and related ‘architectural’ DNA-binding proteins. Trends Biochem Sci. 2001;26(3):167-74.
9. Kang R, Chen R, Zhang Q, Hou W, Wu S, Cao L, et al. HMGB1 in health and disease. Mol Aspects Med. 2014;40:1-116.
10. Tang D, Billiar TR, Lotze MT. A Janus tale of two active high mobility group box 1 (HMGB1) redox states. Mol Med. 2012;18(10):1360-2.
11. Klune JR, Dhupar R, Cardinal J, Billiar TR, Tsung A. HMGB1: endogenous danger signaling. Mol Med. 2008;14(7-8):476-84.
12. Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ. HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol. 2009;28:367-88.
13. Aychek T, Miller K, Sagi-Assif O, Schori C, Salmon-Divon M, Witz IP, et al. E-selectin regulates gene expression in metastatic colorectal carcinoma cells and enhances HMGB1 release. Int J Cancer. 2008;123(8):1741-50.
14. Andersson U, Wang H, Palmblad K, Aveberger AC, Bloom O, Erlandsson-Harris H, et al. High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J Exp Med. 2000;192(4):565-70.
15. Brunetti A, Manfioletti G, Chiefari E, Goldfine ID, Foti D. Transcriptional regulation of human insulin receptor gene by the high-mobility group protein HMGI(Y). FASEB J. 2001;15(2):492-500.
16. Baldassarre G, Battista S, Belletti B, Pierantoni GM, Fusco A, Thakur S, et al. Negative regulation of BRCA1 gene expression by HMGA1 proteins accounts for the reduced BRCA1 protein levels in sporadic breast carcinoma. Mol Cell Biol. 2003;23(7):2225-38.
17. Dong XDE, Ito N, Lotze MT, DeMarco RA, Popovic P, Shand SH, et al. High mobility group box I (HMGB1) release from tumor cells after treatment: implications for development of targeted chemoimmunotherapy. J Immunother. 2007;30(6):596-606.
18. Dolde CE, Mukherjee M, Cho C, Resar LM. HMG-I/Y in human breast cancer cell lines. Breast Cancer Res Treat. 2002;71(3):181-91.
19. Fedele M, Bandiera A, Chiappetta G, Battista S, Viglietto G, Manfioletti G, et al. Human colorectal carcinomas express high levels of high mobility group HMGI(Y) proteins. Cancer Res. 1996;56(8):1896-901.
20. Tarbé N, Evtimova V, Burtscher H, Jarsch M, Alves F, Weidle UH, et al. Transcriptional profiling of cell lines derived from an orthotopic pancreatic tumor model reveals metastasis-associated genes. Anticancer Res. 2001;21(5):3221-8.
21. Leman ES, Madigan MC, Brünagel G, Takaha N, Coffey DS, Getzenberg RH, et al. Nuclear matrix localization of high mobility group protein I(Y) in a transgenic mouse model for prostate cancer. J Cell Biochem. 2003;88(3):599-608.
22. Petit A, Ragu C, Della-Valle V, Bernard OA, Fenaux P, Mozziconacci MJ, et al. NUP98–HMGB3: a novel oncogenic fusion. Leukemia. 2010;24(3):654-8.
23. Passalacqua M, Zicca A, Sparatore B, Patrone M, Melloni E, Pontremoli S, et al. Secretion and binding of HMG1 protein to the external surface of the membrane are required for murine erythroleukemia cell differentiation. FEBS Lett. 1997;400(3):275-9.
24. Zhu H, Wang L, Ruan Y, Zhang Y, Chen W, Xie M, et al. An efficient delivery of DAMPs on the cell surface by the unconventional secretion pathway. Biochem Biophys Res Commun. 2011;404(3):790-5.
25. Hanspal M, Hanspal JS. The association of erythroblasts with macrophages promotes erythroid proliferation and maturation: a 30-kD heparin-binding protein is involved in this contact. Blood. 1994.
26. Maugeri N, Franchini S, Campana L, Baldini M, Ramirez GA, Sabbadini MG, et al. Circulating platelets as a source of the damage-associated molecular pattern HMGB1 in patients with systemic sclerosis. Autoimmunity. 2012;45(8):584-7.
27. Mitroulis I, Kambas K, Chrysanthopoulou A, Skendros P, Mitroulis SA, Ritis K, et al. Neutrophil extracellular trap formation is associated with IL-1β and autophagy-related signaling in gout. PLoS One. 2011;6(12):e29318.
28. Tadie J-M, Bae H-B, Jiang S, Park DW, Bell CP, Yang H, et al. HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4. Am J Physiol Lung Cell Mol Physiol. 2013;304(5):L342-9.
29. Jia L, Clear A, Liu F-T, Li K, Spence P, Ramsay A, et al. Extracellular HMGB1 promotes differentiation of nurse-like cells in chronic lymphocytic leukemia. Blood. 2014;123(11):1709-19.
30. Aneja RK, Tsung A, Sjodin H, Klune JR, Shin JH, Kaczorowski DJ, et al. Preconditioning with high mobility group box 1 (HMGB1) induces lipopolysaccharide (LPS) tolerance. J Leukoc Biol. 2008;84(5):1326-34.
31. Dahlhaus M, Schult C, Lange S, Freund M, Junghanss C, Junghanss C, et al. MicroRNA 181a influences the expression of HMGB1 and CD4 in acute leukemias. Anticancer Res. 2013;33(2):445-52.
32. Kang R, Tang D, Cao L, Yu Y, Zhang G, Xiao X, et al. High mobility group box 1 is increased in children with acute lymphocytic leukemia and stimulates the release of tumor necrosis factor-alpha in leukemic cells. Zhonghua Er Ke Za Zhi. 2007;45(5):329-33.
| Issue | Vol 8, No 1 (2025) | |
| Section | Original Article | |
| DOI | https://doi.org/10.18502/igj.v8i1.17994 | |
| Keywords | ||
| Acute lymphoblastic leukemia (ALL) HMGB1 Polymorphism Sanger Sequencing | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Rayzan E, Farajzadeh Valilou S, Hemmati S, Sadeghi A, Farajifard H, Shahkarami S, Rezaei N. HMGB1 Polymorphisms in Acute Lymphoblastic Leukemia. Immunol Genet J. 2025;8.
