Prognostically significant fusion oncogenes in Pakistani patients with adult acute lymphoblastic leukemia and their association with disease biology and outcome

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 . 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.Noreen Sabir, Zafar Iqbal, Aamer Aleem, Tashfeen Awan, Tahir Naeem, Sultan Asad, Ammara H Tahir, Muhammad Absar, Rana MW Hasanato, Sulman Basit, Muhammad Azhar Chishti, Muhammad Faiyaz Ul-Haque, Ahmad Muktar Khalid, Muhammad Farooq Sabar, Mahmood Rasool, Sajjad Karim, Mahwish Khan, Baila Samreen, Muhammad Hassan Siddiqi, Saba Shahzadi, Sana Shahbaz, Agha Shabbir Ali, Amer Mahmood, Muhammad Akram, Tariq Saeed, Arsalan Saleem, Danish Mohsin, Ijaz Hussain Shah, Muhammad Khalid, Muhammad Asif, Mudassar Iqbal, Tanveer Akhta