Frequency of Chromosomal Abnormalities in Pakistani Adults with Acute Lymphoblastic Leukemia

  • Published : 2014.11.28


Background: The difference in prognosis of adult and childhood acute lymphoblastic leukemia (ALL) can be attributed largely to variation in cytogenetic abnormalities with age groups. Cytogenetic analysis in acute leukemia is now routinely used to assist patient management, particularly in terms of diagnosis, disease monitoring, prognosis and risk stratification. Knowing about cytogenetic profile at the time of diagnosis is important in order to take critical decisions in management of the patients. Aim and Objectives: To determine the frequency of cytogenetic abnormalities in Pakistani adult patients with ALL in order to have insights regarding behavior of the disease. Materials and Methods: A retrospective analysis of all the cases of ALL (${\geq}15$years old) diagnosed at Aga Khan University from January 2006 to June 2014 was performed. Phenotype (B/T lineage) was confirmed in all cases by flow cytometry. Cytogenetic analysis was made for all cases using the trypsin-Giemsa banding technique. Karyotypes were interpreted using the International System for Human Cytogenetic Nomenclature (ISCN) criteria. Results: A total of 166 patients were diagnosed as ALL during the study period, of which 151 samples successfully yielded metaphase chromosomes. The male to female ratio was 3.4:1. The majority (n=120, 72.3%) had a B-cell phenotype. A normal karyotype was present in 51% (n=77) of the cases whereas 49% (n=74) had an abnormal karyotype. Of the abnormal cases, 10% showed Philadelphia chromosome; t(9;22)(q34;q11.2). Other poor prognostic cytogenetic subgroups were t(4;11)(q21;q23), hypodiploidy (35-45 chromosomes) and complex karyotype. Hyperdiploidy (47-57 chromosomes) occurred in 6.6%; all of whom were younger than 30 years. Conclusions: This study showed a relatively low prevalence of Philadelphia chromosome in Pakistani adults with ALL with an increase in frequency with age (p=0.003). The cumulative prevalence of Philadelphianegative poor cytogenetic aberrations in different age groups was not significant (p=0.6).


  1. Chilton L, Buck G, Harrison CJ, et al (2013). High hyperdiploidy among adolescents and adults with acute lymphoblastic leukemia (ALL): cytogenetic features, clinical characteristics and outcome. Leukemia, 28, 1511-8.
  2. Faderl S, O'Brien S, Pui CH, et al (2010). Adult acute lymphoblastic leukemia. Cancer, 116, 1165-76.
  3. Garcia DR, Bhatt S, Manvelyan M, et al (2011). An unusual T-cell childhood acute lymphoblastic leukemia harboring a yet unreported near-tetraploid karyotype. Mol Cytogenet, 4, 20.
  4. Gomez-Segui I, Cervera J, Such E, et al (2012). Prognostic value of cytogenetics in adult patients with Philadelphia-negative acute lymphoblastic leukemia. Ann Hematol, 91, 19-25.
  5. Healey K, Gray SL, Halligan GE, et al (2009). Hyperdiploidy with trisomy 9 and deletion of the CDKN2A locus in T-cell acute lymphoblastic leukemia. Cancer Genet Cytogenet, 190, 121-4.
  6. Jiang Y, Hou J, Zhang Q, et al (2013). The MTHFR C677T polymorphism and risk of acute lymphoblastic leukemia: an updated meta-analysis based on 37 case-control studies. Asian Pac J Cancer Prev, 14, 6357-62.
  7. Jinnai I, Sakura T, Tsuzuki M, et al (2010). Intensified consolidation therapy with dose-escalated doxorubicin did not improve the prognosis of adults with acute lymphoblastic leukemia: the JALSG-ALL97 study. Int J Hematol, 92, 490-502.
  8. Kaspers GJ, Smets LA, Pieters R, et al (1995). Favorable prognosis of hyperdiploid common acute lymphoblastic leukemia may be explained by sensitivity to antimetabolites and other drugs: results of an in vitro study. Blood, 85, 751-6.
  9. Khalid S, Usman M, Adil SN, et al (2007). Pattern of chromosomal abnormalities in adult acute lymphoblastic leukemia. Indian J Pathol Microbiol, 50, 78-81.
  10. Lee HJ, Thompson JE, Wang ES, et al (2011). Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer, 117, 1583-94.
  11. Mishra S, Zhang B, Cunnick JM, et al (2006). Resistance to imatinib of bcr/abl p190 lymphoblastic leukemia cells. Cancer Res, 66, 5387-93.
  12. Moorman AV, Chilton L, Wilkinson J, et al (2010a). A population-based cytogenetic study of adults with acute lymphoblastic leukemia. Blood, 115, 206-14.
  13. Moorman AV, Ensor HM, Richards SM, et al (2010b). Prognostic effect of chromosomal abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: results from the UK Medical Research Council ALL97/99 randomised trial. Lancet Oncol, 11, 429-38.
  14. Pullarkat V, Slovak ML, Kopecky KJ, et al (2008). Impact of cytogenetics on the outcome of adult acute lymphoblastic leukemia: results of Southwest Oncology Group 9400 study. Blood, 111, 2563-72.
  15. Ribera JM, Oriol A (2009). Acute lymphoblastic leukemia in adolescents and young adults. Hematol Oncol Clin North Am, 23, 1033-42.
  16. Shaikh MS, Ali SS, Khurshid M, et al (2014). Chromosomal abnormalities in Pakistani children with acute lymphoblastic leukemia. Asian Pac J Cancer Prev, 15, 3907-9.
  17. Vardiman JW, Thiele Je, Arber DA, et al (2009). The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood, 114, 937-51.
  18. Wang C-X, Wang X, Liu H-B, et al (2014). Aberrant DNA methylation and epigenetic inactivation of hMSH2 decrease overall survival of acute lymphoblastic leukemia patients via modulating cell cycle and apoptosis. Asian Pac J Cancer Prev, 15, 355-62.

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