Comparison of Gene Expression Levels in the p53 Pathway in Blood and Bone Marrow of Healthy Individuals
Yıl 2023,
, 103 - 108, 18.09.2023
Aynur Dağlar Aday
,
Gözde Öztan
,
Ilknur Suer
Öz
Objective: A bone marrow (BM) sample is largely used in the diagnosis and prognosis follow-up of many hematological malignancies. BM aspiration is a more risky and laborious technique compared to blood collection. Together with publications in which the expression levels in BM and peripheral blood (PB) are correlated for many genes, there are also conflicting publications. This may also be due to the physiological and disease state. In this study, we aimed to compare the BM and PB expression levels of genes in the p53 pathway in healthy individuals.
Materials and Methods: The study comprised 23 healthy individuals. The expressions of 22 genes in the p53 pathway were analyzed using the RT2-profiler polymerase chain reaction (PCR) array. The expression levels were normalized to the reference gene β-actin. Then the mRNA expression levels between PB and BM sample groups were compared.
Results: The expression levels of the 20 genes studied were similar between the two groups. Only GADD45 and PTX3 genes were differentially expressed between PB and BM sample groups (p=0.003 and p=0.033, respectively) and those two gene expression levels were strongly correlated (r=0.886, p<0.0001).
Conclusion: When the expressions of 20 genes other than the GADD45 and PTX3 in our panel were evaluated, we suggest that PB largely reflects the p53 pathway gene expression levels in the BM. Therefore, PB may be preferred as an alternative to invasive BM in the analysis of these 20 genes in patients with hematological malignancies.
Kaynakça
- 1. Kruiswijk F, Labuschagne CF, Vousden KH. p53 in survival, death and metabolic health: a lifeguard with a licence to kill. Nat Rev Mol Cell Biol 2015; 16(7): 393-405. google scholar
- 2. Lacroix M, Riscal R, Arena G, Linares LK, Le Cam L. Metabolic functions of the tumor suppressor p53: Implications in normal physiology, metabolic disorders, and cancer. Mol Metab 2020; 33: 2-22. google scholar
- 3. Lahalle A, Lacroix M, De Blasio C, Cisse MY, Linares LK, Le Cam L. The p53 pathway and metabolism: The tree that hides the forest. Cancers (Basel) 2021; 13(1): 133. google scholar
- 4. Cowin SC, Cardoso L. Blood and interstitial flow in the hierarchical pore space architecture of bone tissue. J Biomech 2015; 48(5): 842-54. google scholar
- 5. Schraw JM, Woodhouse JP, Bernhardt MB, Taylor OA, Horton TM, Scheurer ME, et al. Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia. Sci Rep 2021; 11(1): 19613. google scholar
- 6. Lucas D. Structural organization of the bone marrow and its role in hematopoiesis. Curr Opin Hematol 2021; 28(1): 36-42. google scholar
- 7. Banerjee P, Rossi MG, Anghelescu DL, Liu W, Breazeale AM, Reddick WE, et al. Association between anesthesia exposure and neurocognitive and neuroimaging outcomes in long-term survivors of childhood acute lymphoblastic leukemia. JAMA Oncol 2019; 5(10): 1456-63. google scholar
- 8. Holtick U, Albrecht M, Chemnitz JM, Theurich S, Shimabukuro-Vornhagen A, Skoetz N, et al. Comparison of bone marrow versus peripheral blood allogeneic hematopoietic stem cell transplantation for hematological malignancies in adults - a systematic review and meta-analysis. Crit Rev Oncol Hematol 2015; 94(2): 179-88. google scholar
- 9. Pinhel MAS, Noronha NY, Nicoletti CF, Quinhoneiro DCG, Oliveira BAP, Cortes-Oliveira C, et al. Comparison of gene expression profile between blood cells and white adipose tissue of patients with obesity. Nutr Hosp 2017; 34(3): 608-12. google scholar
- 10. Ellis MH, Baraf L, Shaish A, Har-Zahav A, Harats D, Ashur-Fabian O. Alteration of lipids and the transcription of lipid-related genes in myelodysplastic syndromes via a TP53-related pathway. Exp Hematol 2012; 40(7): 540-7. google scholar
- 11. Schittenhelm MM, Illing B, Ahmut F, Rasp KH, Blumenstock G, Döhner K, et al. Attenuated expression of apoptosis stimulating protein of p53-2 (ASPP2) in human acute leukemia is associated with therapy failure. PLoS One 2013; 8(11): e80193. google scholar
- 12. Harris SL, Levine AJ. The p53 pathway: positive and negative feedback loops. Oncogene 2005; 24(17): 2899-908. google scholar
- 13. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, et al. Mutational landscape and significance across 12 major cancer types. Nature 2013; 502(7471): 333-9. google scholar
- 14. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25(4): 402-8. google scholar
- 15. Simabuco FM, Morale MG, Pavan ICB, Morelli AP, Silva FR, Tamura RE. p53 and metabolism: from mechanism to therapeutics. Oncotarget 2018; 9(34): 23780-823. google scholar
- 16. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100(1): 57-70. google scholar
- 17. Ilknur S, Aynur A, Sariman M, Mesut A, Hindilerden IY, Ekmekci SS, et al. Dysregulation of MS4A3 and PRDX5 gene expression in multiple myeloma patients. Int J Hem Oncol 2021; 31(4): 205-13. google scholar
- 18. Öztan G, Aktan M, Palanduz S, İşsever H, Öztürk S, Nikerel E, et al. Relationship between chromosomal aberrations and gene expressions in the p53 pathway in chronic lymphocytic leukemia. Balkan J Med Genet 2020; 23(1): 15-24. google scholar
- 19. Crassini KR, Shen Y, Christopherson R, Stevenson WS, Mulligan S, Best OG. Analysis of mRNA expression in peripheral, bone marrow and lymph node dervied CLL Cells using the nanosting ncounter platform. Blood 2017; 130(1): 4279. google scholar
- 20. Wiestner A, Marti GE, Billings EM, Liu H, Lee E, White T, et al. Differential gene expression in CLL cells from bone marrow and peripheral blood suggests a role of bone marrow stroma in leukemic cell proliferation. Blood 2005; 106(11): 708. google scholar
- 21. Sakhinia E, Farahangpour M, Tholouli E, Liu Yin JA, Hoyland JA, Byers RJ. Comparison of gene-expression profiles in parallel bone marrow and peripheral blood samples in acute myeloid leukaemia by real-time polymerase chain reaction. J Clin Pathol 2006; 59(10): 1059-65. google scholar
- 22. Jiang Q, Zhao XY, Qin YZ, Liu YR, Lai YY, Jiang B, et al. The differences and correlations of BCR-ABL transcripts between peripheral blood and bone marrow assays are associated with the molecular responses in the bone marrow for chronic myelogenous leukemia. Am J Hematol 2012; 87(12): 1065-9. google scholar
- 23. Van Leeuwen-Kerkhoff N, Lundberg K, Westers TM, Kordasti S, Bontkes HJ, Lindstedt M, et al. Human bone marrow-derived myeloid dendritic cells show an immature transcriptional and functional profile compared to their peripheral blood counterparts and separate from Slan+ non-classical monocytes. Front Immunol 2018; 9: 1619. google scholar
- 14. Guo D, Zhao Y, Wang N, You N, Zhu W, Zhang P, et al. GADD45g acts as a novel tumor suppressor, and its activation suggests new combination regimens for the treatment of AML. Blood 2021; 138(6): 464-79. google scholar
- 25. Liebermann DA, Tront JS, Sha X, Mukherjee K, Mohamed-Hadley A, Hoffman B. Gadd45 stress sensors in malignancy and leukemia. Crit Rev Oncog 2011; 16(1-2): 129-40. google scholar
- 26. Wingert S, Thalheimer FB, Haetscher N, Rehage M, Schroeder T, Rieger MA. DNA-damage response gene GADD45A induces differentiation in hematopoietic stem cells without inhibiting cell cycle or survival. Stem Cells 2016; 34(3): 699-710. google scholar
- 27. Yamasawa K, Nio Y, Dong M, Yamaguchi K, Itakura M. Clinicopathological significance of abnormalities in Gadd45 expression and its relationship to p53 in human pancreatic cancer. Clin Cancer Res 2002; 8(8): 2563-9. google scholar
- 28. Garlanda C, Bottazzi B, Magrini E, Inforzato A, Mantovani A. PTX3, a humoral pattern recognition molecule, in innate immunity, Tissue Repair, and Cancer. Physiol Rev 2018; 98(2): 623-39. google scholar
- 29. Inoue K, Kodama T, Daida H. Pentraxin 3: A novel biomarker for inflammatory cardiovascular disease. Int J Vasc Med 2012; 2012: 657025. google scholar
Yıl 2023,
, 103 - 108, 18.09.2023
Aynur Dağlar Aday
,
Gözde Öztan
,
Ilknur Suer
Kaynakça
- 1. Kruiswijk F, Labuschagne CF, Vousden KH. p53 in survival, death and metabolic health: a lifeguard with a licence to kill. Nat Rev Mol Cell Biol 2015; 16(7): 393-405. google scholar
- 2. Lacroix M, Riscal R, Arena G, Linares LK, Le Cam L. Metabolic functions of the tumor suppressor p53: Implications in normal physiology, metabolic disorders, and cancer. Mol Metab 2020; 33: 2-22. google scholar
- 3. Lahalle A, Lacroix M, De Blasio C, Cisse MY, Linares LK, Le Cam L. The p53 pathway and metabolism: The tree that hides the forest. Cancers (Basel) 2021; 13(1): 133. google scholar
- 4. Cowin SC, Cardoso L. Blood and interstitial flow in the hierarchical pore space architecture of bone tissue. J Biomech 2015; 48(5): 842-54. google scholar
- 5. Schraw JM, Woodhouse JP, Bernhardt MB, Taylor OA, Horton TM, Scheurer ME, et al. Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia. Sci Rep 2021; 11(1): 19613. google scholar
- 6. Lucas D. Structural organization of the bone marrow and its role in hematopoiesis. Curr Opin Hematol 2021; 28(1): 36-42. google scholar
- 7. Banerjee P, Rossi MG, Anghelescu DL, Liu W, Breazeale AM, Reddick WE, et al. Association between anesthesia exposure and neurocognitive and neuroimaging outcomes in long-term survivors of childhood acute lymphoblastic leukemia. JAMA Oncol 2019; 5(10): 1456-63. google scholar
- 8. Holtick U, Albrecht M, Chemnitz JM, Theurich S, Shimabukuro-Vornhagen A, Skoetz N, et al. Comparison of bone marrow versus peripheral blood allogeneic hematopoietic stem cell transplantation for hematological malignancies in adults - a systematic review and meta-analysis. Crit Rev Oncol Hematol 2015; 94(2): 179-88. google scholar
- 9. Pinhel MAS, Noronha NY, Nicoletti CF, Quinhoneiro DCG, Oliveira BAP, Cortes-Oliveira C, et al. Comparison of gene expression profile between blood cells and white adipose tissue of patients with obesity. Nutr Hosp 2017; 34(3): 608-12. google scholar
- 10. Ellis MH, Baraf L, Shaish A, Har-Zahav A, Harats D, Ashur-Fabian O. Alteration of lipids and the transcription of lipid-related genes in myelodysplastic syndromes via a TP53-related pathway. Exp Hematol 2012; 40(7): 540-7. google scholar
- 11. Schittenhelm MM, Illing B, Ahmut F, Rasp KH, Blumenstock G, Döhner K, et al. Attenuated expression of apoptosis stimulating protein of p53-2 (ASPP2) in human acute leukemia is associated with therapy failure. PLoS One 2013; 8(11): e80193. google scholar
- 12. Harris SL, Levine AJ. The p53 pathway: positive and negative feedback loops. Oncogene 2005; 24(17): 2899-908. google scholar
- 13. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, et al. Mutational landscape and significance across 12 major cancer types. Nature 2013; 502(7471): 333-9. google scholar
- 14. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25(4): 402-8. google scholar
- 15. Simabuco FM, Morale MG, Pavan ICB, Morelli AP, Silva FR, Tamura RE. p53 and metabolism: from mechanism to therapeutics. Oncotarget 2018; 9(34): 23780-823. google scholar
- 16. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100(1): 57-70. google scholar
- 17. Ilknur S, Aynur A, Sariman M, Mesut A, Hindilerden IY, Ekmekci SS, et al. Dysregulation of MS4A3 and PRDX5 gene expression in multiple myeloma patients. Int J Hem Oncol 2021; 31(4): 205-13. google scholar
- 18. Öztan G, Aktan M, Palanduz S, İşsever H, Öztürk S, Nikerel E, et al. Relationship between chromosomal aberrations and gene expressions in the p53 pathway in chronic lymphocytic leukemia. Balkan J Med Genet 2020; 23(1): 15-24. google scholar
- 19. Crassini KR, Shen Y, Christopherson R, Stevenson WS, Mulligan S, Best OG. Analysis of mRNA expression in peripheral, bone marrow and lymph node dervied CLL Cells using the nanosting ncounter platform. Blood 2017; 130(1): 4279. google scholar
- 20. Wiestner A, Marti GE, Billings EM, Liu H, Lee E, White T, et al. Differential gene expression in CLL cells from bone marrow and peripheral blood suggests a role of bone marrow stroma in leukemic cell proliferation. Blood 2005; 106(11): 708. google scholar
- 21. Sakhinia E, Farahangpour M, Tholouli E, Liu Yin JA, Hoyland JA, Byers RJ. Comparison of gene-expression profiles in parallel bone marrow and peripheral blood samples in acute myeloid leukaemia by real-time polymerase chain reaction. J Clin Pathol 2006; 59(10): 1059-65. google scholar
- 22. Jiang Q, Zhao XY, Qin YZ, Liu YR, Lai YY, Jiang B, et al. The differences and correlations of BCR-ABL transcripts between peripheral blood and bone marrow assays are associated with the molecular responses in the bone marrow for chronic myelogenous leukemia. Am J Hematol 2012; 87(12): 1065-9. google scholar
- 23. Van Leeuwen-Kerkhoff N, Lundberg K, Westers TM, Kordasti S, Bontkes HJ, Lindstedt M, et al. Human bone marrow-derived myeloid dendritic cells show an immature transcriptional and functional profile compared to their peripheral blood counterparts and separate from Slan+ non-classical monocytes. Front Immunol 2018; 9: 1619. google scholar
- 14. Guo D, Zhao Y, Wang N, You N, Zhu W, Zhang P, et al. GADD45g acts as a novel tumor suppressor, and its activation suggests new combination regimens for the treatment of AML. Blood 2021; 138(6): 464-79. google scholar
- 25. Liebermann DA, Tront JS, Sha X, Mukherjee K, Mohamed-Hadley A, Hoffman B. Gadd45 stress sensors in malignancy and leukemia. Crit Rev Oncog 2011; 16(1-2): 129-40. google scholar
- 26. Wingert S, Thalheimer FB, Haetscher N, Rehage M, Schroeder T, Rieger MA. DNA-damage response gene GADD45A induces differentiation in hematopoietic stem cells without inhibiting cell cycle or survival. Stem Cells 2016; 34(3): 699-710. google scholar
- 27. Yamasawa K, Nio Y, Dong M, Yamaguchi K, Itakura M. Clinicopathological significance of abnormalities in Gadd45 expression and its relationship to p53 in human pancreatic cancer. Clin Cancer Res 2002; 8(8): 2563-9. google scholar
- 28. Garlanda C, Bottazzi B, Magrini E, Inforzato A, Mantovani A. PTX3, a humoral pattern recognition molecule, in innate immunity, Tissue Repair, and Cancer. Physiol Rev 2018; 98(2): 623-39. google scholar
- 29. Inoue K, Kodama T, Daida H. Pentraxin 3: A novel biomarker for inflammatory cardiovascular disease. Int J Vasc Med 2012; 2012: 657025. google scholar