title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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±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.
authors: Hematology, Oncology and Pharmacogenetic Engineering Sciences (HOPES) Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punjab, Pakistan.
authors: Tashfeen
authors: T
authors: Awan
authors: Zafar
authors: Z
authors: Iqbal
authors: Aamer
authors: A
authors: Aleem
authors: Noreen
authors: N
authors: Sabir
authors: Muhammad
authors: M
authors: Absar
authors: Mahmood
authors: M
authors: Rasool
authors: Ammara H
authors: AH
authors: Tahir
authors: Sulman
authors: S
authors: Basit
authors: Ahmad Mukhtar
authors: AM
authors: Khalid
authors: Muhammad Farooq
authors: MF
authors: Sabar
authors: Sultan
authors: S
authors: Asad
authors: Agha Shabbir
authors: AS
authors: Ali
authors: Amer
authors: A
authors: Mahmood
authors: Muhammad
authors: M
authors: Akram
authors: Tariq
authors: T
authors: Saeed
authors: Arsalan
authors: A
authors: Saleem
authors: Danish
authors: D
authors: Mohsin
authors: Ijaz Hussain
authors: IH
authors: Shah
authors: Muhammad
authors: M
authors: Khalid
authors: Muhammad
authors: M
authors: Asif
authors: Riazul
authors: R
authors: Haq
authors: Mudassar
authors: M
authors: Iqbal
authors: Tanveer
authors: T
authors: Akhtar
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010154:Pakistan; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D015996:Survival Rate; D016896:Treatment Outcome; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D016044:Fusion Proteins, bcr-abl; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion; C113855:MLL-AF4 fusion protein, human; C547584:SIL-TAL1 fusion protein, human; C543638:TCF3-PBX1 fusion protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein