Five Most Common Prognostically Important FusionOncogenes are Detected in the Majority of Pakistani Pediatric Acute Lymphoblastic Leukemia Patients and are Strongly Associated with Disease Biology and Treatment Outcome

Background and
Objectives: Acute lymphoblastic leukemia (ALL) is a complex genetic disease involvingmany fusion oncogenes (FO) having prognostic significance. The frequency of various FO can vary in differentethnic groups, with important implications for prognosis, drug selection and treatment outcome.
Method: Westudied fusion oncogenes in 101 pediatric ALL patients using interphase FISH and RT-PCR, and their associationswith 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 foundin 89/101 (88.1%) patients. Frequency of BCR-ABL was 44.5% (45/101). BCR-ABL positive patients had asignificantly lower survival (43.7±4.24 weeks) and higher white cell count as compared to others, except patientswith MLL-AF4. The highest relapse-free survival was documented with ETV6-RUNX1 (14.2 months) followedclosely by those cases in which no gene was detected (13.100). RFS with BCR-ABL, MLL-AF4, TCF3-PBX1and SIL-TAL1 was less than 10 months (8.0, 3.6, 5.5 and 8.1 months, respectively).
Conclusions: This is the firststudy from Pakistan correlating molecular markers with disease biology and treatment outcome in pediatricALL. It revealed the highest reported frequency of BCR-ABL FO in pediatric ALL, associated with poor overallsurvival. Our data indicate an immediate need for incorporation of tyrosine kinase inhibitors in the treatmentof BCR-ABL+ pediatric ALL in this population and the development of facilities for stem cell transplantation.