Detection of BCR/ABL, MLL/AF4 and TEL/AML1 hybrid genes and monitoring of minimal residual disease in pediatric patients with acute lymphoblastic leukemia
Abstract
BACKGROUND: The BCR/ABL and MLL/AF4 fusion genes--resulting from t(9;22)(q34;q11) and t(4;11)(q21;q23) translocations, respectively--are considered as a high risk prognostic factors in children with acute lymphoblastic leukaemia (ALL). Their presence in malignant cells indicates patient for the most intensive antileukaemic therapy regardless of the other criteria.
In contrast, the most common non-random chromosomal aberration in paediatric ALL--translocation t(12;21)(q12;q22)--is associated with a favourable prognosis. The examination of these rearrangements is important for the stratification of patients to the risk groups and also provides the most sensitive and specific tool for minimal residual disease (MRD) follow-up.
METHODS AND RESULTS: This study comprises 241 patients with ALL from Czech and Slovak Republics younger than 18 years at diagnosis. They were examined for presence of m-RNA of fusion genes BCR/ABL, MLL/AF4 and TEL/AML1 by reverse transcriptase-polymerase chain reaction (RT-PCR) method.
Seven out of 197 (3.6%) carried MLL/AF4 fusion gene, but among infants it was 56% (5 out of 9). BCR/ABL positivity was found in 2.5% (7 out of 240) and TEL/AML1 in 21.7% (41 out of 189) cases.
Event free survival (EFS) curves demonstrate the clinical impact of these hybrid genes on patients' prognosis. Moreover, we present the possibility of the monitoring of MRD levels in follow-up samples of these patients.
CONCLUSIONS: All particular rearrangements were found only in a cohort of patients with B-precursor ALL (or hybrid leukaemia), which constitutes 85% of our group. Presence of BCR/ABL or MLL/AF4 fusion gene is associated with poor prognosis and is indispensable condition for correct stratification of patients to the risk groups according to treatment protocols.
Hybrid gene TEL/AML1 defines subgroup of children with better prognosis and due to its high frequency provides us with a very useful tool for MRD detection.