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; Iqbal, Zafar; Aleem, Aamer; Sabir, Noreen; Absar, Muhammad; Rasool, Mahmood; Tahir, Ammara H.; Basit, Sulman; Khalid, Ahmad Mukhtar; Sabar, Muhammad Farooq; Asad, Sultan; Ali, Agha Shabbir; Mahmood, Amer; Akram, Muhammad; Saeed, Tariq; Saleem, Arsalan; Mohsin, Danish; Shah, Ijaz Hussain; Khalid, Muhammad; Asif, Muhammad; Haq, Riazul; Iqbal, Mudassar; Akhtar, Tanveer

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저자정보: Awan, Tashfeen (Hematology, Oncology and Pharmacogenetic Engineering Sciences [HOPES] Group, Health Sciences Laboratories, Faculty of Biological Sciences, Department of Zoology, University of the Punja) 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 Punj) Rasool, Mahmood (Centre of Excellence in Genomic Medicine Research, King) Tahir, Ammara H. Basit, Sulman Khalid, Ahmad Mukhtar Sabar, Muhammad Farooq Asad, Sultan Ali, Agha Shabbir Mahmood, Amer Akram, Muhammad Saeed, Tariq Saleem, Arsalan Mohsin, Danish Shah, Ijaz Hussain Khalid, Muhammad Asif, Muhammad Haq, Riazul Iqbal, Mudassar Akhtar, Tanveer

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제13권 제11호

발행연도: 2012.1

수록면: 5,469 - 5,475 (7page)

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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.

#Acute lymphoblastic leukemia #pediatric ALL #fusion oncogenes #Pakistan

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Awan, Tashfeen

소속기관 Hematology, Oncology and Pharmacogenetic Engineering Sciences Group, Health Sciences Laboratories, F