Abstract:
Acute lymphoblastic leukemia (ALL) is a complex genetic disease involving many
fusion oncogenes having prognostic significance. The frequency of various fusion
oncogenes can vary in different ethnic groups, with important implications for
prognosis, drug selection and treatment outcome. We studied fusion oncogenes in 101
pediatric ALL patients using RT-PCR and interphase FISH, and their associations
with clinical features and treatment outcome. Five most common fusion genes i.e.
BCR-ABL t (22; 9), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) TCF3-PBX1 (t 1;
19), and SIL-TAL1 (del 1p32) were found in 88.1% (89/101) 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, SIL-TAL1 and TCF3-PBX1 was
less than 10 months (8.0, 3.6, 5.5 and 8.1 months, respectively). 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
fusion gene in pediatric ALL, associated with poor overall survival. Present data
indicated 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.
