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Cytogenetic Profile of De Novo B lineage Acute Lymphoblastic Leukemia: Determination of Frequency, Distribution Pattern and Identification of Rare and Novel Chromosomal Aberrations in Indian Patients

  • Published : 2015.11.04

Abstract

Background: Chromosomal aberrations identified in acute lymphoblastic leukemia (ALL) have an important role in disease diagnosis, prognosis and management. Information on karyotype and associated clinical parameters are essential to physicians for planning cancer control interventions in different geographical regions. Materials and Methods: In this study, we present the overall frequency and distribution patterns of chromosomal aberrations in both children and adult de novo B lineage ALL Indian patients using conventional cytogenetics, interphase FISH and multiplex RT-PCR. Results: Among the 215 subjects, cytogenetic results were achieved in 172 (80%) patients; normal karyotype represented 37.2% and abnormal 62.8% with a distribution as follows: 15.3% hypodiploidy; 10.3% hyperdiploidy; 15.8% t(9;22); 9.8% t(1;19); 3.7% t(12;21); 2.8% t(4;11); 2.8% complex karyotypes. Apart from these, we observed several novel, rare and common chromosomal rearrangements. Also, FISH studies using LSI extra-signal dual-color probes revealed additional structural or numerical changes. Conclusions: These results demonstrate cytogenetic heterogeneity of ALL and confirm that the incidence of chromosomal abnormalities varies considerably. To the best of our knowledge, this is one of the largest reported series of cytogenetic investigations in Indian B-lineage ALL cases. In addition, ongoing cytogenetic studies are warranted in larger groups of B-lineage ALL cases to identify newly acquired chromosomal abnormalities that may contribute to disease diagnosis and management.

Keywords

References

  1. Alonso CN, Gallego MS, Rossi JG, et al (2012). RT-PCR diagnosis of recurrent rearrangements in pediatric acute lymphoblastic leukemia in Argentina. Leuk Res, 36, 704-8. https://doi.org/10.1016/j.leukres.2011.12.003
  2. Amare P, Gladstone B, Varghese C, Pai S, Advani S (1999). Clinical Significance of Cytogenetic Findings at Diagnosis and in Remission in Childhood and Adult Acute Lymphoblastic Leukemia: Experience from India. Cancer Genet Cytogenet, 110, 44-53. https://doi.org/10.1016/S0165-4608(98)00179-4
  3. Arora RS, Eden TOB, Kapoor G (2009). Epidemiology of childhood cancer in India. Indian J Cancer, 46, 264-73. https://doi.org/10.4103/0019-509X.55546
  4. Awan T, Iqbal Z, Aleem A, et al (2012). Five most common prognostically important fusion oncogenes are detected in the majority of Pakistani pediatric acute lymphoblastic leukemia patients and are strongly associated with disease biology and treatment outcome. Asian Pac J Cancer Prev, 13, 5469-75. https://doi.org/10.7314/APJCP.2012.13.11.5469
  5. Bhandari P, Ahmad F, Dalvi R, et al (2014). Molecular cytogenetic investigations in a novel chromosomal abnormality of t(10;15)(q22;q22) in a pediatric precursorb- acute lymphoblastic leukemia patient. J Hematol Oncol Res, 1, 28-33. https://doi.org/10.14302/issn.2372-6601.jhor-13-358
  6. Bhatia P, Binota J, Varma N, et al (2012). Incidence of common chimeric fusion transcripts in B-cell acute lymphoblastic leukemia: an Indian perspective. Acta Haematol, 128, 17-9. https://doi.org/10.1159/000338260
  7. Brigaudeau C, Bilhou-Nabera C (1998). del(6q) abnormalities in lymphoid malignancies. Atlas Genet Cytogenet Oncol Haematol, 3, 33-5.
  8. Campbell LJ, Martinow A, Michael PM, et al (1999). Correlation of cytogenetics, BCR-ABL PCR studies and fluorescence in situ hybridisation (FISH) in adult acute lymphoblastic leukaemia. Aust N Z J Med, 29, 707-12. https://doi.org/10.1111/j.1445-5994.1999.tb01619.x
  9. Ceppi F, Brown A, Betts DR, Niggli F, Popovic MB (2009). Cytogenetic characterization of childhood acute lymphoblastic leukemia in Nicaragua. Pediatr Blood Cancer, 53, 1238-41. https://doi.org/10.1002/pbc.22169
  10. Chen B, Wang Y-Y, Shen Y, et al (2012). Newly diagnosed acute lymphoblastic leukemia in China (I): abnormal genetic patterns in 1346 childhood and adult cases and their comparison with the reports from Western countries. Leukemia, 26, 1608-16. https://doi.org/10.1038/leu.2012.26
  11. De Braekeleer E, Basinko A, Douet-Guilbert N, et al (2010). Cytogenetics in pre-B and B-cell acute lymphoblastic leukemia: a study of 208 patients diagnosed between 1981 and 2008. Cancer Genet Cytogenet, 200, 8-15. https://doi.org/10.1016/j.cancergencyto.2010.03.004
  12. Fauzdar A, Jain D, Mishra M, et al (2010). Molecular cytogenetic study in pediatric b-lineage acute lymphoblastic leukemia (BCP-ALL): A collaborative study group from North India. J Clin Oncol.
  13. Gaynon PS, Trigg ME, Heerema NA, et al (2000). Children’s Cancer Group trials in childhood acute lymphoblastic leukemia: 1983-1995. Leukemia, 14, 2223-33. https://doi.org/10.1038/sj.leu.2401939
  14. GFCH (1996). Cytogenetic abnormalities in adult acute lymphoblastic leukemia: correlations with hematologic findings outcome. A collaborative study of the group français de cytogenetique hematologique. Blood, 87, 3135-42.
  15. Hann I, Vora A, Harrison G, et al (2001). Determinants of outcome after intensified therapy of childhood lymphoblastic leukaemia: results from medical research council united kingdom acute lymphoblastic leukaemia XI protocol. Br J Haematol, 113, 103-14. https://doi.org/10.1046/j.1365-2141.2001.02668.x
  16. Harrison CJ, Haas O, Harbott J, et al (2010). Detection of prognostically relevant genetic abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: recommendations from the biology and diagnosis committee of the international berlin-frankfurt-munster study group. Br J Haematol, 151, 132-42. https://doi.org/10.1111/j.1365-2141.2010.08314.x
  17. Heerema N (2000). 12p rearrangements in ALL. Atlas Genet Cytogenet Oncol Haematol, 4, 20-1.
  18. Heerema NA, Nachman JB, Sather HN, et al (1999). Hypodiploidy with less than 45 chromosomes confers adverse risk in childhood acute lymphoblastic leukemia: a report from the children’s cancer group. Blood, 94, 4036-45.
  19. Hill A, Short MA, Varghese C, et al (2005).The t(12:21) is underrepresented in childhood B-lineage acute lymphoblastic leukemia in Kerala, Southern India. Haematologica, 90, 414-6.
  20. Hunger SP, Lu X, Devidas M, et al (2012). Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children’s oncology group. J Clin Oncol, 30, 1663-9. https://doi.org/10.1200/JCO.2011.37.8018
  21. Iacobucci I, Papayannidis C, Lonetti A, et al (2012). Cytogenetic and molecular predictors of outcome in acute lymphocytic leukemia: recent developments. Curr Hematol Malig Rep, 7, 133-43. https://doi.org/10.1007/s11899-012-0122-5
  22. Jimenez-Morales S, Miranda-Peralta E, Saldana-Alvarez Y, et al (2008). BCR-ABL, ETV6-RUNX1 and E2A-PBX1: prevalence of the most common acute lymphoblastic leukemia fusion genes in Mexican patients. Leuk Res, 32, 1518-22. https://doi.org/10.1016/j.leukres.2008.03.021
  23. Johansson B, Billstrom R, Kristoffersson U, et al (1997). Deletion of chromosome arm 3p in hematologic malignancies. Leukemia, 11, 1207-13. https://doi.org/10.1038/sj.leu.2400718
  24. Mancini M, Scappaticci D, Cimino G, et al (2005). A comprehensive genetic classification of adult acute lymphoblastic leukemia (ALL): analysis of the GIMEMA 0496 protocol. Blood, 105, 3434-41. https://doi.org/10.1182/blood-2004-07-2922
  25. Mazloumi SHM, Madhumathi DS, Appaji L, Prasannakumari (2012). Combined study of cytogenetics and fluorescence in situ hybridization (FISH) analysis in childhood acute lymphoblastic leukemia (ALL) in a tertiary cancer centre in South India. Asian Pac J Cancer Prev, 13, 3825-7. https://doi.org/10.7314/APJCP.2012.13.8.3825
  26. Mesquita DR, Cordoba JC, Magalhaes IQ, et al (2009). Molecular and chromosomal mutations among children with B-lineage lymphoblastic leukemia in Brazil’s Federal District. Genet Mol Res, 8, 345-53. https://doi.org/10.4238/vol8-1gmr582
  27. Moorman AV, Chilton L, Wilkinson J, et al (2010a). A population-based cytogenetic study of adults with acute lymphoblastic leukemia. Blood, 115, 206-14. https://doi.org/10.1182/blood-2009-07-232124
  28. Moorman AV, Ensor HM, Richards SM, et al (2010). 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. https://doi.org/10.1016/S1470-2045(10)70066-8
  29. Nahi H, Hägglund H, Ahlgren T, et al (2008). An investigation into whether deletions in 9p reflect prognosis in adult precursor B-cell acute lymphoblastic leukemia: a multicenter study of 381 patients. Haematologica, 93, 1734-8. https://doi.org/10.3324/haematol.13227
  30. Pallisgaard N, Hokland P, Riishoj DC, Pedersen B, Jorgensen P (1998). Multiplex reverse transcription-polymerase chain reaction for simultaneous screening of 29 translocations and chromosomal aberrations in acute leukemia. Blood, 92, 574-88.
  31. Pandita A, Harish R, Digra SK, et al (2015). Molecular cytogenetics in childhood acute lymphoblastic leukemia: a hospital-based observational study. Clin Med Insights Oncol, 9, 39-42.
  32. Polampalli S, Prabhash K, Amare P, et al (2011). Role of RT-PCR and FISH in diagnosis and monitoring of acute promyelocytic leukemia. Indian J Cancer, 48, 60. https://doi.org/10.4103/0019-509X.75831
  33. Pui C-H, Carroll A, Raimondi S, et al (1992). Isochromosomes in childhood acute lymphoblastic leukemia: A collaborative study of 83 cases. Blood, 79, 2384-91.
  34. Pui C-H, Chessells JM, Camitta B, et al (2003). Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements. Leukemia, 17, 700-6. https://doi.org/10.1038/sj.leu.2402883
  35. Pui C-H, Evans WE (2006). Treatment of acute lymphoblastic leukemia. N Engl J Med, 354, 166-78. https://doi.org/10.1056/NEJMra052603
  36. Sabir N, Iqbal Z, Aleem A, et al (2012). Prognostically significant fusion oncogenes in Pakistani patients with adult acute lymphoblastic leukemia and their association with disease biology and outcome. Asian Pac J Cancer Prev, 13, 3349-55. https://doi.org/10.7314/APJCP.2012.13.7.3349
  37. Safaei A, Shahryari J, Farzaneh MR, Tabibi N, Hosseini M (2013). Cytogenetic findings of patients with acute lymphoblastic leukemia in fars province. Iran J Med Sci, 38, 301-7.
  38. Santamaria-Quesada C, Vargas M, Venegas P, et al (2009). Molecular and epidemiologic findings of childhood acute leukemia in Costa Rica. J Pediatr Hematol Oncol, 31, 131-5. https://doi.org/10.1097/MPH.0b013e31818c919e
  39. Sazawal S, Bhatia K, Gutierrez MI, et al (2004). Paucity of TELAML 1 translocation, by multiplex RT-PCR, in B-lineage acute lymphoblastic leukemia (ALL) in Indian patients. Am J Hematol, 76, 80-2. https://doi.org/10.1002/ajh.20000
  40. Secker-Walker LM, Prentice HG, Durrant J, et al (1997). Cytogenetics adds independent prognostic information in adults with acute lymphoblastic leukaemia on MRC trial UKALL XA. MRC Adult Leukaemia Working Party. Br J Haematol, 96, 601-10. https://doi.org/10.1046/j.1365-2141.1997.d01-2053.x
  41. Shaffer LG, McGowan-Jordan J, Schmid M, editors (2013). ISCN 2013: An International System for Human Cytogenetic Nomenclature. Karger, Basel.
  42. Shaikh MS, Ali SS, Khurshid M, Fadoo Z (2014). Chromosomal abnormalities in Pakistani children with acute lymphoblastic leukemia. Asian Pac J Cancer Prev, 15, 3907-9. https://doi.org/10.7314/APJCP.2014.15.9.3907
  43. Siraj AK, Kamat S, Gutierrez MI, et al (2003). Frequencies of the major subgroups of precursor B-cell acute lymphoblastic leukemia in Indian children differ from the West. Leukemia, 17, 1192-3. https://doi.org/10.1038/sj.leu.2402931
  44. Stark B, Jeison M, Gobuzov R, et al (2001). Near haploid childhood acute lymphoblastic leukemia masked by hyperdiploid line: detection by fluorescence in situ hybridization. Cancer Genet Cytogenet, 128, 108-13. https://doi.org/10.1016/S0165-4608(01)00411-3
  45. Walters R, Kantarjian HM, Keating MJ, et al (1990). The importance of cytogenetic studies in adult acute lymphocytic leukemia. Am J Med, 89, 579-87. https://doi.org/10.1016/0002-9343(90)90175-D
  46. Watanabe N, Kobayashi H, Ichiji O, et al (2003). Cryptic insertion and translocation or nondividing leukemic cells disclosed by FISH analysis in infant acute leukemia with discrepant molecular and cytogenetic findings. Leukemia, 17, 876-82. https://doi.org/10.1038/sj.leu.2402900

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