DOI QR코드

DOI QR Code

Prognostically Significant Fusion Oncogenes in Pakistani Patients with Adult Acute Lymphoblastic Leukemia and their Association with Disease Biology and Outcome

  • Sabir, Noreen (Hematology, Oncology and Pharmacogenetic Engineering Sciences Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Iqbal, Zafar (Hematology, Oncology and Pharmacogenetic Engineering Sciences Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Aleem, Aamer (Hematology, Oncology and Pharmacogenetic Engineering Sciences Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Awan, Tashfeen (Hematology, Oncology and Pharmacogenetic Engineering Sciences Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Naeem, Tahir (Hematology, Oncology and Pharmacogenetic Engineering Sciences Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Asad, Sultan (Centre for Advanced Molecular Biology, University of Lahore) ;
  • Tahir, Ammara H (Hematology, Oncology and Pharmacogenetic Engineering Sciences Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Absar, Muhammad (Hematology, Oncology and Pharmacogenetic Engineering Sciences Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Hasanato, Rana MW (Department of Medicine, Microbiology Section, College of Medicine and King Khalid University Hospital, King Saud University) ;
  • Basit, Sulman (Department of Medicine, Biochemistry Research Section, College of Medicine and King Khalid University Hospital, King Saud University) ;
  • Chishti, Muhammad Azhar (Department of Medicine, Biochemistry Research Section, College of Medicine and King Khalid University Hospital, King Saud University) ;
  • Ul-Haque, Muhammad Faiyaz (Department of Pathology, Molecular Genetic Pathology, College of Medicine and King Khalid University Hospital, King Saud University) ;
  • Khalid, Ahmad Muktar (School of Biology Sciences, University of Sargodha) ;
  • Sabar, Muhammad Farooq (Centre for Advanced Molecular Biology, University of Lahore) ;
  • Rasool, Mahmood (Centre of Excellence in Genomic Medicine Research, King Abdulaziz University) ;
  • Karim, Sajjad (Centre of Excellence in Genomic Medicine Research, King Abdulaziz University) ;
  • Khan, Mahwish (Hematology, Oncology and Pharmacogenetic Engineering Sciences Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Samreen, Baila (Hematology, Oncology and Pharmacogenetic Engineering Sciences Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Akram, Afia M (Hematology, Oncology and Pharmacogenetic Engineering Sciences Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Siddiqi, Muhammad Hassan (Hematology, Oncology and Pharmacogenetic Engineering Sciences Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Shahzadi, Saba (Hematology, Oncology and Pharmacogenetic Engineering Sciences Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Shahbaz, Sana (Hematology, Oncology and Pharmacogenetic Engineering Sciences Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Ali, Agha Shabbir (Post Graduate Medical Institute & Institute of Child Health)
  • 발행 : 2012.07.31

초록

Background and objectives: Chromosomal abnormalities play an important role in genesis of acute lymphoblastic leukemia (ALL) and have prognostic implications. Five major risk stratifying fusion genes in ALL are BCR-ABL, MLL-AF4, ETV6-RUNX11, E2A-PBX1 and SIL-TAL1. This work aimed to detect common chromosomal translocations and associated fusion oncogenes in adult ALL patients and study their relationship with clinical features and treatment outcome. Methods: We studied fusion oncogenes in 104 adult ALL patients using RT-PCR and interphase-FISH at diagnosis and their association with clinical characteristics and treatment outcome. Results: Five most common fusion genes i.e. BCR-ABL (t 9; 22), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (Del 1p32) were found in 82/104 (79%) patients. TCF3-PBX1 fusion gene was associated with lymphadenopathy, SIL-TAL1 positive patients had frequent organomegaly and usually presented with a platelets count of less than $50{\times}10^9/l$. Survival of patients with fusion gene ETV6-RUNX1 was better when compared to patients harboring other genes. MLL-AF4 and BCR-ABL positivity characterized a subset of adult ALL patients with aggressive clinical behaviour and a poor outcome. Conclusions: This is the first study from Pakistan which investigated the frequency of5 fusion oncogenes in adult ALL patients, and their association with clinical features, treatment response and outcome. Frequencies of some of the oncogenes were different from those reported elsewhere and they appear to be associated with distinct clinical characteristics and treatment outcome. This information will help in the prognostic stratification and risk adapted management of adult ALL patients.

키워드

참고문헌

  1. Andreasson P, Schwaller J, Anastasiadou E, et al (2001). The expression of ETV6/CBFA2 (TEL/AML1) is not sufficient for the transformation of hematopoietic cell lines in vitro or the induction of hematologic disease in vivo. Cancer Genet Cytogenet, 130, 93-104. https://doi.org/10.1016/S0165-4608(01)00518-0
  2. Bassan R (2005). Evolving strategies for the management of high-risk adult acute lymphoblastic leukemia. Haematologica, 90, 1299.
  3. Burmeister T. Gokbuget N, Schwartz S, et al (2010). Clinical features and prognostic implications of TCF3-PBX1 and ETV6-RUNX1 in adult acute lymphoblastic leukemia. Haematologica, 95, 241-6. https://doi.org/10.3324/haematol.2009.011346
  4. Debaraj PE, Foroni L, Janossy G, et al (1995). Expression of the E2A-PBX1 fusion transcripts in t (1; 19) (q23; p13) and der (19) t (1; 19) at diagnosis and in remission of acute lymphoblastic leukemia with different B lineage immunophenotypes. Leukemia, 9, 821-5.
  5. Faderl S, Kantarjian HM, Talpaz M, Estrov Z (1998). Clinical significance of cytogenetic abnormalities in adult acute lymphoblastic leukemia. Blood, 91, 3995-4019.
  6. Faiz M, Iqbal QJ, Qureshi A (2011). High prevalence of BCR-ABL fusion transcripts with poor prognostic impact among adult ALL patients: report from Pakistan. Asia Pac J Clin Oncol, 7, 47-55.
  7. Fielding AK (2010). How I treat Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood, 116, 3409-17. https://doi.org/10.1182/blood-2010-01-242750
  8. Foa R, Vitale A, Mancini M, et al (2003). E2A-PBX1 fusion in adult acute lymphoblastic leukaemia: biological and clinical features. Br J Haematol, 120, 484-7. https://doi.org/10.1046/j.1365-2141.2003.04113.x
  9. Harrison CJ, Foroni L (2002). Cytogenetics and molecular genetics of acute lymphoblastic leukemia. Rev Clin Exp Hematol, 6, 91-113. https://doi.org/10.1046/j.1468-0734.2002.00069.x
  10. 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
  11. Iqbal Z (2006). Frequency of chromosomal abnormalities and corresponding fusion oncogenes in acute lymphoblastic leukemia (ALL) patients of Pakistan and its implication in differential diagnosis and prognosis of leukemia. Haematologica, 91, 65.
  12. Iqbal Z, Tanveer A (2006) Incidence of different fusion oncogenes in acute lymphoblastic leukemia (ALL) patients from Pakistan: possible implication in differential diagnosis, prognosis, treatment and management of ALL. Haematologica, 91, 64.
  13. Iqbal Z, Akhtar T, Iqbal M, et al (2009). First comprehensive report of strong interplay of genetic and environmental factors as well as high degree of ethnic and geographical variations in biology of leukemia as manifested by frequencies of common fusion oncogenes of prognostic significance associated with different Leukemic subtypes in Pakistani population. In: Online proceedings American Association for Cancer Research 100TH Annual Meeting, April 18-22, Colorado, Denver.
  14. 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
  15. Moorman AV, Harrison CJ, Buck GA, et al (2007). Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the medical research council (MRC) UKALLXII/eastern cooperative oncology group (ECOG) 2993 trial. Blood, 109, 3189-97. https://doi.org/10.1182/blood-2006-10-051912
  16. Pui CH, Evans WE (2006). Treatment of acute lymphoblastic leukemia. N Engl J Med, 354, 166-78. https://doi.org/10.1056/NEJMra052603
  17. Pui CH, Robison LL, Look AT (2008). Acute lymphoblastic leukaemia. Lancet, 371, 1030-43. https://doi.org/10.1016/S0140-6736(08)60457-2
  18. Pui CH, Sandlund JT, Pei D, et al (2004). Improved outcome for children with acute lymphoblastic leukemia: results of total therapy study XIIIB at St jude children's research hospital. Blood, 104, 2690-6. https://doi.org/10.1182/blood-2004-04-1616
  19. Soverini S, Colarossi S, Gnani A, et al (2007). Resistance to dasatinib in Philadelphia-positive leukemia patients and the presence or the selection of mutations at residues 315 and 317 in the BCR-ABL kinase domain. Haematologica, 92, 401-4. https://doi.org/10.3324/haematol.10822
  20. The groupe franGais de cytoghetique hematologique (1996). Cytogenetic abnormalities in adult acute lymphoblastic leukemia: correlations with hematologic findings and outcome. Blood, 87, 3135-42.
  21. Thomas X, Boiron JM, Huguet F, et al (2004). Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol, 22, 4075-86. https://doi.org/10.1200/JCO.2004.10.050
  22. Van Dongen JJ, Macintyre EA, Gabert JA, et al (1999). Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Report of the BIOMED-1 Concerted Action: investigation of minimal residual disease in acute leukemia. Leukemia, 13, 1901-28. https://doi.org/10.1038/sj.leu.2401592
  23. Xing H, Yang X, Liu T, et al (2012). The study of resistant mechanisms and reversal in an imatinib resistant Ph+ acute lymphoblastic leukemia cell line. Leuk Res, 36, 509-13. https://doi.org/10.1016/j.leukres.2011.12.018

피인용 문헌

  1. 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 vol.13, pp.11, 2012, https://doi.org/10.7314/APJCP.2012.13.11.5469
  2. Molecular Genetic Studies on 167 Pediatric ALL Patients from Different Areas of Pakistan Confirm a Low Frequency of the Favorable Prognosis Fusion Oncogene TEL-AML1 (t 12; 21) in Underdeveloped Countries of the Region vol.15, pp.8, 2014, https://doi.org/10.7314/APJCP.2014.15.8.3541
  3. New Haplotypes of the ATP Synthase Subunit 6 Gene of Mitochondrial DNA are Associated with Acute Lymphoblastic Leukemia in Saudi Arabia vol.15, pp.23, 2015, https://doi.org/10.7314/APJCP.2014.15.23.10433
  4. 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 vol.16, pp.16, 2015, https://doi.org/10.7314/APJCP.2015.16.16.7219
  5. Importance of FISH combined with Morphology, Immunophenotype and Cytogenetic Analysis of Childhood/Adult Acute Lymphoblastic Leukemia in Omani Patients vol.16, pp.16, 2015, https://doi.org/10.7314/APJCP.2015.16.16.7343
  6. Acute Lymphoblastic Leukemia in Adults - an Analysis of 51 Cases from a Tertiary Care Center in Pakistan vol.17, pp.4, 2016, https://doi.org/10.7314/APJCP.2016.17.4.2307
  7. Frequency and clinical impact of ETV6/RUNX1, AF4-MLL, and BCR/ABL fusion genes on features of acute lymphoblastic leukemia at presentation vol.19, pp.2, 2016, https://doi.org/10.4103/1119-3077.164351
  8. Downregulation of SATB1 increases the invasiveness of Jurkat cell via activation of the WNT/β-catenin signaling pathway in vitro vol.37, pp.6, 2016, https://doi.org/10.1007/s13277-015-4638-x
  9. Tyrosine kinase inhibitors: potential use and safety considerations in HIV-1 infection vol.16, pp.5, 2017, https://doi.org/10.1080/14740338.2017.1313224