Hira Qadir, Nadia Nasir, Nida Qadir, Salman Naseem Adil, Hammad Tanzeem, Areesha Qadir


Background: Chronic lymphocytic leukaemia (CLL), an indolent but malignant lymphoproliferative disorder, is characterized by unregulated and uninhibited growth of mature monoclonal lymphocytes, with deletion of 17p containing TP53 gene being the most important prognostic factor. TP53 mutations, reported in 10% of CLL cases, seem to have a direct correlation to a more advanced stage and aggressive transformation of CLL. Methods:This was a retrospective cross-sectional descriptive study limited to a period from 1st June 2013 to 30th June 2016, conducted at Section of haematology, Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi. One thirty-nine cases of CLL received for TP53 mutation analysis at the Aga Khan University hospital clinical Laboratory were included in the study. Five ml of whole blood or one ml of bone marrow aspirate sample in EDTA tube was collected for the detection of TP53 mutation by the FISH technique. Statistical package for social sciences 21 was used for data entry and analysis. Results: Of the 139 chronic lymphocytic leukaemia patients, 43 (31%) were females and 96 (69%) were males. The mean age of all patients was 56.3±10.84 years. Tp53 gene mutation in patients with chronic lymphocytic leukaemia was found only in 19(13.7%) patients. Among these patients 15(10.9%) were male and 04(2.9%) were females. Age and gender were not statistically significant with Tp53 mutation with a p-Value > 0.05 at a 95% confidence interval. Conclusion:  In a cohort of Pakistani patients with Chronic lymphocytic leukaemia, TP53 gene mutation was found in 19(13.7%).

Keywords: Chronic lymphocytic leukaemia; CLL; Tumour suppressor gene; TP53; Fluorescence in Situ hybridization; FISH

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Smith A, Howell D, Patmore R, Jack A, Roman E. Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network. Br J Cancer 2011;105(11):1684–92.

Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63(1):11–30.

Kyo K, Sameshima S, Tanaka Y, Murayama K, Shimano S, Kojima M, et al. Rectal cancer associated with chronic lymphocytic leukaemia. J Gastroenterol 2004;39(5):479–83.

Wu SJ, Huang SY, Lin CT, Lin YJ, Chang CJ, Tien HF. The incidence of chronic lymphocytic leukaemia in Taiwan, 1986-2005: a distinct increasing trend with birth-cohort effect. Blood J Am Soc Hematol 2010;116(22):4430–5.

Yang C, Zhang X. Incidence survey of leukaemia in China. Chin Med Sci J 1991;6(2):65–70.

Cordone I, Masi S, Mauro FR, Soddu S, Morsilli O, Valentini T, et al. p53 expression in B-cell chronic lymphocytic leukaemia: a marker of disease progression and poor prognosis. Blood J Am Soc Hematol 1998;91(11):4342–9.

Damle RN, Wasil T, Fais F, Ghiotto F, Valetto A, Allen SL, et al. Ig V Gene Mutation Status and CD38 Expression As Novel Prognostic Indicators in Chronic Lymphocytic Leukaemia: Presented in part at the 40th Annual Meeting of The American Society of Hematology, held in Miami Beach, FL, December 4-8, 1998. Blood J Am Soc Hematol 1999;94(6):1840–7.

Crespo M, Bosch F, Villamor N, Bellosillo B, Colomer D, Rozman M, Marcé S, et al. ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukaemia. N Engl J Med 2003;348(18):1764–75.

Zenz T, Kröber A, Scherer K, Häbe S, Bühler A, Benner A, et al. Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukaemia: results from a detailed genetic characterization with long-term follow-up. Blood J Am Soc Hematol 2008;112(8):3322–9.

Oscier DG, Gardiner AC, Mould SJ, Glide S, Davis ZA, Ibbotson RE, et al. Multivariate analysis of prognostic factors in CLL: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors. Blood J Am Soc Hematol 2002;100(4):1177–84.

Song H, Xu Y. Gain of function of p53 cancer mutants in disrupting critical DNA damage response pathways. Cell Cycle 2007;6(13):1570–3.

Wilson WH, Teruya-Feldstein J, Fest T, Harris C, Steinberg SM, Jaffe ES, et al. Relationship of p53, bcl-2, and tumor proliferation to clinical drug resistance in non-Hodgkin's lymphomas. Blood J Am Soc Hematol 1997;89(2):601–9.

Cano I, Martinez J, Quevedo E, Pinilla J, Martin-Recio A, Rodriguez A, et al. Trisomy 12 and p53 deletion in chronic lymphocytic leukaemia detected by fluorescence in situ hybridization: association with morphology and resistance to conventional chemotherapy. Cancer Genet Cytogenet 1996;90(2):118–24.

Lens D, JJC De Schouwer P, Hamoudi RA, Abdul-Rauf M, Farahat N, Matutes E, et al. p53 abnormalities in B-cell prolymphocytic leukaemia. Blood J Am Soc Hematol 1997;89(6):2015–23.

Dong HJ, Zhou LT, Zhu DX, Wang DM, Fang C, Zhu HY, et al. The prognostic significance of TP53 mutations in Chinese patients with chronic lymphocytic leukaemia is independent of del (17p13). Ann Hematol 2011;90(6):709–17.

Zenz T, Eichhorst B, Busch R, Denzel T, Habe S, Winkler D, et al. TP53 mutation and survival in chronic lymphocytic leukaemia. J Clin Oncol 2010;28(29):4473–9.

Gonzalez D, Martinez P, Wade R, Hockley SL, Brito-Babapulle V, Oscier DG, et al. Mutational status of the TP53 gene as a predictor of response and survival in CLL patients with and without 17p deletion. 2008.

Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukaemia: a report from the International Workshop on Chronic Lymphocytic Leukaemia updating the National Cancer Institute–Working Group 1996 guidelines. Blood J Am Soc Hematol 2008;111(12):5446–56.

Byrd JC, Gribben JG, Peterson BL, Grever MR, Lozanski G, Lucas DM, et al. Select high-risk genetic features predict earlier progression following chemoimmunotherapy with fludarabine and rituximab in chronic lymphocytic leukaemia: justification for risk-adapted therapy. J Clin Oncol 2006;24(3):437–43.

Mulligan SP, Tam CS. Chronic lymphocytic leukaemia: diagnosis and clinical staging. Future Medicine Ltd, 2012.

Agrawal N, Naithani R, Mahapatra M, Panigrahi I, Kumar R, Pati HP, et al. Chronic lymphocytic leukaemia in India-A clinico-hematological profile. Hematology 2007;12(3):229–33.

Hernández JA, Land KJ, McKenna RW. Leukaemias, myeloma, and other lymphoreticular neoplasms. Cancer 1995;75(Suppl 1):381–94.

Yamamoto JF, Goodman MT. Patterns of leukaemia incidence in the United States by subtype and demographic characteristics, 1997–2002. Cancer Causes Control 2008;19(4):379–90.

Kobayashi T, Kita K, Ohno T, Shirakawa S. Chronic lymphocytic leukaemia in Japan. Rinsho ketsueki 1990;31(5):554–63.

Haenszel W, Kurihara M. Studies of Japanese migrants. I. Mortality from cancer and other diseases among Japanese in the United States. J Nat Cancer Inst 1968;40(1):43–68.

Yanagihara ET, Blaisdell RK, Hayashi T, Lukes RJ. Malignant lymphoma in Hawaii‐Japanese: a retrospective morphologic survey. Hematol Oncol 1989;7(3):219–32.

Reddy KS. Chronic lymphocytic leukaemia profiled for prognosis using a fluorescence in situ hybridisation panel. Br J Haematol 2006;132(6):705–22.

Grubor V, Krasnitz A, Troge JE, Meth JL, Lakshmi B, Kendall JT, et al. Novel genomic alterations and clonal evolution in chronic lymphocytic leukaemia revealed by representational oligonucleotide microarray analysis (ROMA). Blood J Am Soc Hematol 2009;113(6):1294–303.

Rossi D, Khiabanian H, Spina V, Ciardullo C, Bruscaggin A, Famà R, et al. Clinical impact of small TP53 mutated subclones in chronic lymphocytic leukaemia. Blood J Am Soc Hematol 2014;123(14):2139–47.


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