Abstract
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. We studied fusion oncogenes in 101 pediatric ALL patients using interphase FISH and RT-PCR, and their associations with clinical features and treatment outcome. 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±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). 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.
Highlights
The incidence of acute lymphocytic leukemia (ALL) is not uniform around the world
The frequency of various fusion oncogenes (FO) can vary in different ethnic groups, with important implications for prognosis, drug selection and treatment outcome
We studied fusion oncogenes in 101 pediatric Acute lymphoblastic leukemia (ALL) patients using interphase FISH and RT-PCR, and their associations with clinical features and treatment outcome
Summary
The incidence of acute lymphocytic leukemia (ALL) is not uniform around the world It varies from 0.9-4.7 per 100,000 children per year (Zhang et al, 2011).The infant mortality rate in Pakistan is 71% which is one of the highest in the world (Ashraf, 2012). Molecular analysis of the common genetic alterations in leukemic cells has contributed greatly to our understanding of the pathogenesis and prognosis of ALL (Iqbal et al, 2007; Pui et al, 2008). The presence of recurrent genetic markers represents subtypes of the disease which may have different etiologies (Iqbal et al, 2007; Kuiper et al, 2007; Treviño et al, 2009; Pui et al, 2011). According to the best of our knowledge this is the first community-based study from Pakistan focused on exploring the prevalence of five common ALL fusion oncogenes in children with ALL and their correlation with the disease biology and treatment outcome
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