title: Prognostically significant fusion oncogenes in Pakistani patients with adult acute lymphoblastic leukemia and their association with disease biology and outcome.
abstract: OBJECTIVE
  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-TAL positive patients had frequent organomegaly and usually presented with a platelets count of less than 50 x10(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 of 5 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.
authors.affiliation: Faculty of Biological Sciences, Department of Zoology, University of the Punjab, Lahore, Pakistan.
authors.forename: Noreen
authors.initials: N
authors.lastname: Sabir
authors.forename: Zafar
authors.initials: Z
authors.lastname: Iqbal
authors.forename: Aamer
authors.initials: A
authors.lastname: Aleem
authors.forename: Tashfeen
authors.initials: T
authors.lastname: Awan
authors.forename: Tahir
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authors.lastname: Naeem
authors.forename: Sultan
authors.initials: S
authors.lastname: Asad
authors.forename: Ammara H
authors.initials: AH
authors.lastname: Tahir
authors.forename: Muhammad
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authors.lastname: Absar
authors.forename: Rana M W
authors.initials: RM
authors.lastname: Hasanato
authors.forename: Sulman
authors.initials: S
authors.lastname: Basit
authors.forename: Muhammad Azhar
authors.initials: MA
authors.lastname: Chishti
authors.forename: Muhammad
authors.initials: M
authors.lastname: Faiyaz Ul-Haque
authors.forename: Ahmad Muktar
authors.initials: AM
authors.lastname: Khalid
authors.forename: Muhammad Farooq
authors.initials: MF
authors.lastname: Sabar
authors.forename: Mahmood
authors.initials: M
authors.lastname: Rasool
authors.forename: Sajjad
authors.initials: S
authors.lastname: Karim
authors.forename: Mahwish
authors.initials: M
authors.lastname: Khan
authors.forename: Baila
authors.initials: B
authors.lastname: Samreen
authors.forename: Afia M
authors.initials: AM
authors.lastname: Akram
authors.forename: Muhammad Hassan
authors.initials: MH
authors.lastname: Siddiqi
authors.forename: Saba
authors.initials: S
authors.lastname: Shahzadi
authors.forename: Sana
authors.initials: S
authors.lastname: Shahbaz
authors.forename: Agha Shabbir
authors.initials: AS
authors.lastname: Ali
authors.forename: Amer
authors.initials: A
authors.lastname: Mahmood
authors.forename: Muhammad
authors.initials: M
authors.lastname: Akram
authors.forename: Tariq
authors.initials: T
authors.lastname: Saeed
authors.forename: Arsalan
authors.initials: A
authors.lastname: Saleem
authors.forename: Danish
authors.initials: D
authors.lastname: Mohsin
authors.forename: Ijaz Hussain
authors.initials: IH
authors.lastname: Shah
authors.forename: Muhammad
authors.initials: M
authors.lastname: Khalid
authors.forename: Muhammad
authors.initials: M
authors.lastname: Asif
authors.forename: Mudassar
authors.initials: M
authors.lastname: Iqbal
authors.forename: Tanveer
authors.initials: T
authors.lastname: Akhtar
mesh_terms: D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000473:pathology; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008206:Lymphatic Diseases / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D050596:Oncogene Fusion; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D010154:Pakistan; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D014178:Translocation, Genetic / Q000235:genetics; D016896:Treatment Outcome; D055815:Young Adult; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D016044:Fusion Proteins, bcr-abl; D018398:Homeodomain Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion; C113855:MLL-AF4 fusion protein, human; C547584:SIL-TAL1 fusion protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein; C089847:E2A-Pbx1 fusion protein