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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

  • Awan, Tashfeen (Hematology, Oncology and Pharmacogenetic Engineering Sciences (HOPES) Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Iqbal, Zafar (Hematology, Oncology and Pharmacogenetic Engineering Sciences (HOPES) Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Aleem, Aamer (Hematology, Oncology and Pharmacogenetic Engineering Sciences (HOPES) Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Sabir, Noreen (Hematology, Oncology and Pharmacogenetic Engineering Sciences (HOPES) Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Absar, Muhammad (Hematology, Oncology and Pharmacogenetic Engineering Sciences (HOPES) Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Rasool, Mahmood (Centre of Excellence in Genomic Medicine Research, King Abdulaziz University) ;
  • Tahir, Ammara H. (Hematology, Oncology and Pharmacogenetic Engineering Sciences (HOPES) Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Basit, Sulman (Biochemistry Research Section, Department of Anatomy, College of Medicine and King Khalid University Hospital, King Saud University) ;
  • Khalid, Ahmad Mukhtar (School of Biological Sciences, University of Sargodha) ;
  • Sabar, Muhammad Farooq (Centre for Advanced Molecular Biology & National Centre of Excellence in Molecular Biology) ;
  • Asad, Sultan (Centre for Advanced Molecular Biology & National Centre of Excellence in Molecular Biology) ;
  • Ali, Agha Shabbir (Post Graduate Medical Institute & Institute of Child Health) ;
  • Mahmood, Amer (Embryonic Stem Cell Unit, Department of Anatomy, College of Medicine and King Khalid University Hospital, King Saud University) ;
  • Akram, Muhammad (Department of Oncology, Allama Iqbal Medical College and Jinnah Hospital) ;
  • Saeed, Tariq (Department of Oncology, Allama Iqbal Medical College and Jinnah Hospital) ;
  • Saleem, Arsalan (University of Health Sciences) ;
  • Mohsin, Danish (University of Health Sciences) ;
  • Shah, Ijaz Hussain (Department of Oncology, Punjab Medical College and Allied Hospital) ;
  • Khalid, Muhammad (Department of Oncology, Punjab Medical College and Allied Hospital) ;
  • Asif, Muhammad (Department of Biotechnology and Informatics, (BUITEMS)) ;
  • Haq, Riazul (Health Centre, University of Texas San Antonio) ;
  • Iqbal, Mudassar (Hematology, Oncology and Pharmacogenetic Engineering Sciences (HOPES) Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab) ;
  • Akhtar, Tanveer (Hematology, Oncology and Pharmacogenetic Engineering Sciences (HOPES) Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab)
  • Published : 2012.11.30

Abstract

Background and Objectives: Acute lymphoblastic leukemia (ALL) is a complex genetic disease involving many fusion oncogenes (FO) having prognostic significance. The frequency of various FO can vary in different ethnic groups, with important implications for prognosis, drug selection and treatment outcome. Method: We studied fusion oncogenes in 101 pediatric ALL patients using interphase FISH and RT-PCR, and their associations with clinical features and treatment outcome. Results: Five most common fusion genes i.e. BCR-ABL t (22; 9), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (del 1p32) were found in 89/101 (88.1%) patients. Frequency of BCR-ABL was 44.5% (45/101). BCR-ABL positive patients had a significantly lower survival ($43.7{\pm}4.24$ weeks) and higher white cell count as compared to others, except patients with MLL-AF4. The highest relapse-free survival was documented with ETV6-RUNX1 (14.2 months) followed closely by those cases in which no gene was detected (13.100). RFS with BCR-ABL, MLL-AF4, TCF3-PBX1 and SIL-TAL1 was less than 10 months (8.0, 3.6, 5.5 and 8.1 months, respectively). Conclusions: This is the first study from Pakistan correlating molecular markers with disease biology and treatment outcome in pediatric ALL. It revealed the highest reported frequency of BCR-ABL FO in pediatric ALL, associated with poor overall survival. Our data indicate an immediate need for incorporation of tyrosine kinase inhibitors in the treatment of BCR-ABL+ pediatric ALL in this population and the development of facilities for stem cell transplantation.

Keywords

References

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