Increased Turnover of Beta 2 Microglobulin in Circulation serves as Diagnostic and Prognostic Marker for Malignant Lymphoma; A Case Control Predictive Model for Lymphoma Diagnosis

Beta 2 microglobulin as a diagnostic and prognostic marker

Authors

  • Tamseela Mumtaz Department of Zoology, Govt. College for Women University, Faisalabad, Pakistan
  • Muhammad Amir Iqbal Institute of Zoology, University of the Punjab, Lahore, Pakistan
  • Nabila Roohi Institute of Zoology, University of the Punjab, Lahore, Pakistan
  • Muhammad Waheed Akhtar School of Biological Sciences, University of the Punjab, Lahore, Pakistan

DOI:

https://doi.org/10.54393/pjhs.v4i05.757

Keywords:

Diagnostic marker; beta 2 microglobulin; Hodgkin’s lymphoma; Non-Hodgkin’s lymphoma; MICA 1; ELISA

Abstract

Indolent and aggressive hematopoietic cancer shed lot of Beta 2 microglobulin in interstitial fluid thus increasing the level of B2M in hematological malignancies. Objectives: To set forward B2M as potential biomarker for the detection and stage of malignant lymphoma. Methods:  Serum of newly diagnosed Hodgkin’s and non-Hodgkin’s lymphoma patients presented to physician prior to any surgical or medicinal treatment were collected and evaluated through sandwich type of ELISA for the possible elevation of B2M. B2M concentrations in healthy individual’s serum (control group) were also detected. Mean values of B2M in all three groups were compared by applying one-way analysis of variance to determine the significant difference. Results: The serum of Hodgkin’s Lymphoma patients depicted 5 folds higher B2M concentration than the healthy subjects, while NHL showed more concentration of circulating B2M where it was 6-fold higher than healthy subjects. Moreover, the advanced stage of the disease with involvement of distant site or organ portrayed increase shedding of MICA 1 chain in circulating blood than localized or regional disease. Conclusions: Elevated serum B2M concentrations in blood surely a sign of neoplastic disease involving nucleated cell like lymphoma and its enhanced expression in distantly spreading disease proved it as a prognostic marker as well

References

Berggård I and Bearn AG. Isolation and properties of a low molecular weight β2-globulin occurring in human biological fluids. Journal of Biological Chemistry. 1968 Aug; 243(15): 4095-103. doi: 10.1016/S0021-9258(18)93284-9.

Grey HM, Kubo RT, Colon SM, Poulik MD, Cresswell P, Springer T, et al. The small subunit of HL-A antigens is β2-microglobulin. The Journal of Experimental Medicine. 1973 Nov; 138(6): 1608. doi: 10.1084/jem.138.6.1608.

Nakamuro K, Tanigaki N, Pressman D. Multiple common properties of human β2-microglobulin and the common portion fragment derived from HL-A antigen molecules. Proceedings of the National Academy of Sciences. 1973 Oct; 70(10): 2863-5. doi: 10.1073/pnas.70.10.2863.

Cresswell P, Turner MJ, Strominger JL. Papain-solubilized HL-A antigens from cultured human lymphocytes contain two peptide fragments. Proceedings of the National Academy of Sciences. 1973 May; 70(5): 1603-7. doi: 10.1073/pnas.70.5.1603.

Bernier GM. β2‐microglobulin: Structure, function and significance. Vox Sanguinis. 1980 Jun; 38(6): 323-7. doi: 10.1159/000467018.

Shi C, Zhu Y, Su Y, Chung LW, Cheng T. β2-Microglobulin: emerging as a promising cancer therapeutic target. Drug Discovery Today. 2009 Jan; 14(1-2): 25-30. doi: 10.1016/j.drudis.2008.11.001.

Crisp AJ, Coughlan RJ, Mackintosh D, Clark B, Panayi GS. Beta 2 microglobulin plasma levels reflect disease activity in rheumatoid arthritis. The Journal of Rheumatology. 1983 Dec; 10(6): 954-6.

Toth DF, Raderer M, Wadsak W, Karanikas G. Beta-2 microglobulin as a diagnostic parameter in non-Hodgkin lymphoma: A comparative study with FDG-PET. Anticancer Research. 2013 Aug; 33(8): 3341-5.

Yoo C, Yoon DH, Suh C. Serum beta-2 microglobulin in malignant lymphomas: an old but powerful prognostic factor. Blood Research. 2014 Sep; 49 (3): 148. doi: 10.5045/br.2014.49.3.148.

Collins GS, Reitsma JB, Altman DG, Moons KG. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement. Journal of British Surgery. 2015 Feb; 102(3): 148-58. doi: 10.1002/bjs.9736.

Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, et al. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. Clinical Chemistry. 2015 Dec; 61(12): 1446-52. doi: 10.1373/clinchem.2015.246280.

Mumtaz T, Roohi N, Akhtar MW. Incidence and clinical manifestation of lymphoma in Central Punjab. Pakistan Journal of Zoology. 2012 Oct; 44(5): 1367-72.

Federico M, Bellei M, Marcheselli L, Luminari S, Lopez-Guillermo A, Vitolo U, et al. Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. Journal of Clinical Oncology. 2009 Sep; 27(27): 4555-62. doi: 10.1200/JCO.2008.21.3991.

Seo S, Hong JY, Yoon S, Yoo C, Park JH, Lee JB, et al. Prognostic significance of serum beta-2 microglobulin in patients with diffuse large B-cell lymphoma in the rituximab era. Oncotarget. 2016 Nov; 7(47): 76934. doi: 10.18632/oncotarget.12734.

Hagberg H, Killander A, Simonsson B. Serum β2‐microglobulin in malignant lymphoma. Cancer. 1983 Jun; 51(12): 2220-5. doi: 10.1002/1097-0142(19830615)51:12<2220::AID-CNCR2820511212>3.0.CO;2-A.

Anderson H, Scarffe JH, Swindell R, Crowther D. Serum β2-microglobulin in patients with non-Hodgkin's lymphoma. European Journal of Cancer and Clinical Oncology. 1983 Mar; 19(3): 327-31. doi: 10.1016/0277-5379(83)90129-3.

Hahn JS, Lee S, Chong SY, Min YH, Ko YW. Eight-year experience of malignant lymphoma: survival and prognostic factors. Yonsei Medical Journal. 1997 Oct; 38(5): 270-84. doi: 10.3349/ymj.1997.38.5.270.

Dimopoulos MA, Cabanillas F, Lee JJ, Swan F, Fuller L, Allen PK, et al. Prognostic role of serum beta 2-microglobulin in Hodgkin's disease. Journal of Clinical Oncology. 1993 Jun; 11(6): 1108-11. doi: 10.1200/JCO.1993.11.6.1108.

Chronowski GM, Wilder RB, Tucker SL, Ha CS, Sarris AH, Hagemeister FB, et al. An elevated serum beta‐2‐microglobulin level is an adverse prognostic factor for overall survival in patients with early‐stage Hodgkin disease. Cancer: Interdisciplinary International Journal of the American Cancer Society. 2002 Dec; 95(12): 2534-8. doi: 10.1002/cncr.10998.

Barca-Hernando M, Muñoz-Martin AJ, Rios-Herranz E, Garcia-Escobar I, Beato C, Font C, et al. Case-Control Analysis of the Impact of Anemia on Quality of Life in Patients with Cancer: A Qca Study Analysis. Cancers. 2021 May; 13(11): 2517. doi: 10.3390/cancers13112517.

Itoh K, Kinoshita T, Watanabe T, Yoshimura K, Okamoto R, Chou T, et al. Prognostic analysis and a new risk model for Hodgkin lymphoma in Japan. International Journal of Hematology. 2010 Apr; 91(3): 446-55. doi: 10.1007/s12185-010-0533-9.

Yang J, Zhang X, Wang J, Qian J, Zhang L, Wang M, et al. Anti–β2-microglobulin monoclonal antibodies induce apoptosis in myeloma cells by recruiting MHC class I to and excluding growth and survival cytokine receptors from lipid rafts. Blood, The Journal of the American Society of Hematology. 2007 Oct; 110(8): 3028-35. doi: 10.1182/blood-2007-06-094417.

Vassilakopoulos TP, Nadali G, Angelopoulou MK, Siakantaris MP, Dimopoulou MN, Kontopidou FN, et al. The prognostic significance of beta (2)-microglobulin in patients with Hodgkin's lymphoma. Haematologica. 2002 Jan; 87(7): 701-8.

Vassilakopoulos TP, Arapaki MP, Diamantopoulos PT, Angelopoulou MK, Nadali G, Tsourouflis G, et al. The Prognostic Significance of Serum Beta-2 Microglobulin (sβ2m) Levels in Patients with Hodgkin Lymphoma (HL): Final Analysis on 915 Patients Treated with ABVD or Equivalent (ABVDeq) Chemotherapy or Combined Modality Therapy (CT/CMT) Focusing to the Determination of Optimal Cut-Offs. Blood. 2022 Nov; 140(Supplement 1): 12016-7. doi: 10.1182/blood-2022-169972.

Saddiwal R, Hebbale M, Sane VD, Hiremutt D, Gupta R, Merchant Y. Estimation of serum beta 2-microglobulin levels in individuals exposed to carcinogens: clinical study in Indian population. Journal of Maxillofacial and Oral Surgery. 2017 Mar; 16: 53-7. doi:10.1007/s12663-016-0914-6.

Nakajima Y, Tomita N, Watanabe R, Ishiyama Y, Yamamoto E, Ishibashi D, et al. Prognostic significance of serum beta-2 microglobulin level in Hodgkin lymphoma treated with ABVD-based therapy. Medical Oncology. 2014 Sep; 31(9): 185. doi: 10.1007/s12032-014-0185-3.

Miyashita K, Tomita N, Taguri M, Suzuki T, Ishiyama Y, Ishii Y, et al. Beta-2 microglobulin is a strong prognostic factor in patients with DLBCL receiving R-CHOP therapy. Leukemia Research. 2015 Nov; 39(11): 1187-91. doi: 10.1016/j.leukres.2015.08.016.

Johnson PW, Whelan J, Longhurst S, Stepniewska K, Matthews J, Amess J, et al. β-2 microglobulin: a prognostic factor in diffuse aggressive non-Hodgkin's lymphomas. British Journal of Cancer. 1993 Apr; 67(4): 792-7. doi: 10.1038/bjc.1993.144.

Alici S, Bavbek SE, Kaytan E, Eralp Y, Onat H. Prognostic factors in localized aggressive non-Hodgkin’s lymphoma. American Journal of Clinical Oncology. 2003 Feb; 26(1): 1-5. doi: 10.1097/00000421-200302000-00001.

López-Guillermo A, Colomo L, Jiménez M, Bosch F, Villamor N, Arenillas L, et al. Diffuse large B-cell lymphoma: clinical and biological characterization and outcome according to the nodal or extranodal primary origin. Journal of Clinical Oncology. 2005 Apr; 23(12): 2797-804. doi: 10.1200/JCO.2005.07.155.

Romaguera JE, Fayad L, Rodriguez MA, Broglio KR, Hagemeister FB, Pro B, et al. High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine. Journal of Clinical Oncology. 2005 Oct; 23(28): 7013-23. doi: 10.1200/JCO.2005.01.1825.

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Published

2023-05-31
CITATION
DOI: 10.54393/pjhs.v4i05.757
Published: 2023-05-31

How to Cite

Mumtaz, T., Iqbal, M. A., Roohi, N., & Akhtar, M. W. (2023). Increased Turnover of Beta 2 Microglobulin in Circulation serves as Diagnostic and Prognostic Marker for Malignant Lymphoma; A Case Control Predictive Model for Lymphoma Diagnosis: Beta 2 microglobulin as a diagnostic and prognostic marker. Pakistan Journal of Health Sciences, 4(05), 160–165. https://doi.org/10.54393/pjhs.v4i05.757

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