Measurements of p53 Isoform Protein Concentration and Energetic Levels in Cells of CLL Using Enzymatic Methods

Aurelian Udristioiu; Alexandru Giubelan; Ana Velcea; Liviu Martin; Manole Cojocaru; Ioan-Ovidiu Gheorghe

doi:10.23958/ijirms/vol10-i05/2073

Abstract

Background/Objectives: Aim of this works of researches proposed the detection of the isoform p53 protein in the patients with Chronic Lymphocytic Leukemia of type B, (CLL-B), performed using the quantitative sandwich Enzyme linked immunoassay ELISA for the direct detection of the p53 isoform protein, a product of the mutant P53 gene. Methods: Additionally, the cellular energy levels, particularly in CLL-B, were measured using a bioluminescence method. The study employed a quantitative sandwich ELISA method for the direct detection of the p53 isoform protein, a product of the mutant P53 gene Adenosine triphosphate, (ATP), was measured using the standard bioluminescence principle on an automatic LKB analyzer with an ATP monitoring reagent. Results: The presence of isoform p53 protein in the studied group was calculated at 17%. Unfavorable evolution and transformation of CLL into Diffuse Large B-Cell Lymphoma (DLBCL) were observed in 3.5% of the cases. In such as malignant diseases, increased ATP values were observed in Chronic Lymphatic Leukemia in values of 4.30-4.55 μM ATP, (Normal energy in B Cells: x̄ = 0.35 μM ATP, (SD = 0.42). Conclusion: Maturation state of the clonal tumor and the prognosis of patients with CLL depend on anaerobic metabolism and the expression of the p53 protein isoform.

Keywords

chronic lymphocytic leukemiaP53 geneisoform p53 proteinCD-5 receptorDiffuse Large Lymphomaadenosine triphosphate

References

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Warburg O. On the origin of cancer cells. Science. 1956;123(3191):309-14.Google Scholar ↗
Giardina TM, Steer JH, Lo SZ, Joyce DA. Uncoupling protein-2 accumulates rapidly in the inner mitochondrial membrane during mitochondrial reactive oxygen stress in macrophages. Biochim Biophys Acta. 2008;1777(2):118-29.Google Scholar ↗
Horimoto M, Resnick MB, Konkin TA, Routhier J, Wands JR, Baffy G. Expression of uncoupling protein-2 in human colon cancer. Clin Cancer Res. 2004;10(18 Pt 1):6203-07.Google Scholar ↗
Randle PJ, England PJ, DGoogle Scholar ↗
Enton RM. Control of the tricarboxylate cycle and its interactions with glycolysis during acetate utilization in rat heart. Biochem J. 1970;117(4):677-95.Google Scholar ↗
Glassman AB, Hayes KJ. The value of fluorescence in situ hybridization in the diagnosis and prognosis of chronic lymphocytic leukemia. Cancer Genet Cytogenet. 2015; 158:88-91.Google Scholar ↗
Nielsen BP, Gupta R, Dewalt DW, Paternoster SF, Rosen ST, Peterson LC. Chronic lymphocytic leukemia FISH panel: impact on the diagnosis. Am J Clin Pathol. 2007;128(2):323-32.Google Scholar ↗
Gillies RJ, Robey I, Gatenby RA. Causes and consequences of increased glucose metabolism of cancers. J Nucl Med. 2008;49(Suppl 2):24S-2S.Google Scholar ↗
Denko NC. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer. 2008;8(9):705-13.Google Scholar ↗
Udristioiu A, Cristina F, Andrei PM. High concentration of anaerobic ATP implicated in aborted apoptosis from CLL. Lab Med. 2010;41(4):203-8.Google Scholar ↗
Sabapathy K. The contrived mutant p53 oncogene - beyond loss of functions. Sci Rep. 2015; 7:99913.Google Scholar ↗
Bennett JM. Practical diagnosis of hematologic disorders: molecular prognostic factors in non-Hodgkin lymphoma, chronic lymphocytic leukemia. In: [Book Title]. Chicago: ASCP Press; 2006:615-71.Google Scholar ↗
Whibley C, Pharoah P, Hollstein M. p53 polymorphism: cancer implications. Nat Rev Cancer. 2009; 2:95-107.Google Scholar ↗

[refR-1] Hainaut P, Hollstein M. p53 and human cancer: the first ten thousand mutations. In: Advances in Cancer Research. London: Academic Press; 2000:81-123.Google Scholar ↗

[refR-2] Soussi T. The p53 tumor suppressor gene: from molecular biology to clinical investigation. Ann N Y Acad Sci. 2000; 910:121-39.Google Scholar ↗

[refR-3] Gottlieb E, Vousden KH. p53 regulation of metabolic pathways. Cold Spring Harb Perspect Biol. 2010;4:a001040.Google Scholar ↗

[refR-4] Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19(11):1423-37.Google Scholar ↗

[refR-5] Martemucci G, Costagliola C, Mariano M, D’Andrea L, Napolitano P, D’Alessandro AG. Free radical properties, source and targets, antioxidant consumption and health. Oxygen. 2022;2(2):48-78.Google Scholar ↗

[refR-6] Chapman AG, Fall L, Atkinson DE. Adenylate energy charge in Escherichia coli during growth and starvation. J Bacteriol. 1971;108(3):1072-86.Google Scholar ↗

[refR-7] Shahjahani M, Mohammadias J, Noroozi F, Seghatoleslam M, Shahrabi S, Saba F, et al. Molecular basis of chronic lymphocytic leukemia diagnosis and prognosis. Cell Oncol. 2015;38(2):93-109.Google Scholar ↗

[refR-8] Hirschey MD, DeBerardinis RJ, Diehl AME, Drew JE, Frezza C, Green MF, et al. Dysregulated metabolism contributes to oncogenesis. Semin Cancer Biol. 2015;35(Suppl): S129-S150.Google Scholar ↗

[refR-9] Warburg O. On the origin of cancer cells. Science. 1956;123(3191):309-14.Google Scholar ↗

[refR-10] Giardina TM, Steer JH, Lo SZ, Joyce DA. Uncoupling protein-2 accumulates rapidly in the inner mitochondrial membrane during mitochondrial reactive oxygen stress in macrophages. Biochim Biophys Acta. 2008;1777(2):118-29.Google Scholar ↗

[refR-11] Horimoto M, Resnick MB, Konkin TA, Routhier J, Wands JR, Baffy G. Expression of uncoupling protein-2 in human colon cancer. Clin Cancer Res. 2004;10(18 Pt 1):6203-07.Google Scholar ↗

[refR-12] Randle PJ, England PJ, DGoogle Scholar ↗

[refR-13] Enton RM. Control of the tricarboxylate cycle and its interactions with glycolysis during acetate utilization in rat heart. Biochem J. 1970;117(4):677-95.Google Scholar ↗

[refR-14] Glassman AB, Hayes KJ. The value of fluorescence in situ hybridization in the diagnosis and prognosis of chronic lymphocytic leukemia. Cancer Genet Cytogenet. 2015; 158:88-91.Google Scholar ↗

[refR-15] Nielsen BP, Gupta R, Dewalt DW, Paternoster SF, Rosen ST, Peterson LC. Chronic lymphocytic leukemia FISH panel: impact on the diagnosis. Am J Clin Pathol. 2007;128(2):323-32.Google Scholar ↗

[refR-16] Gillies RJ, Robey I, Gatenby RA. Causes and consequences of increased glucose metabolism of cancers. J Nucl Med. 2008;49(Suppl 2):24S-2S.Google Scholar ↗

[refR-17] Denko NC. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer. 2008;8(9):705-13.Google Scholar ↗

[refR-18] Udristioiu A, Cristina F, Andrei PM. High concentration of anaerobic ATP implicated in aborted apoptosis from CLL. Lab Med. 2010;41(4):203-8.Google Scholar ↗

[refR-19] Sabapathy K. The contrived mutant p53 oncogene - beyond loss of functions. Sci Rep. 2015; 7:99913.Google Scholar ↗

[refR-20] Bennett JM. Practical diagnosis of hematologic disorders: molecular prognostic factors in non-Hodgkin lymphoma, chronic lymphocytic leukemia. In: [Book Title]. Chicago: ASCP Press; 2006:615-71.Google Scholar ↗

[refR-21] Whibley C, Pharoah P, Hollstein M. p53 polymorphism: cancer implications. Nat Rev Cancer. 2009; 2:95-107.Google Scholar ↗