Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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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)
  • Published : 2012.07.31
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Abstract

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.

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References

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