Abstract
Objectives We have analyzed t(12;21)(p13:q22) in an attempt to evaluate the frequency and prognostic significance of TEL-AML1 fusion gene in patients with childhood CD 10 positive B-ALL by fluorescence in situ hybridization (FISH). Also, we have monitored the prognostic value of this gene as a minimal residual disease (MRD).MethodsAll bone marrow samples of eighty patients diagnosed as CD 10 positive B-ALL in South Egypt Cancer Institute were evaluated by fluorescence in situ hybridization (FISH) for t(12;21) in newly diagnosed cases and after morphological complete remission as a minimal residual disease (MRD). We determined the prognostic significance of TEL-AML1 fusion represented by disease course and survival.ResultsTEL-AML1 fusion gene was positive in (37.5%) in newly diagnosed patients. There was a significant correlation between TEL-AML1 fusion gene both at diagnosis (r = 0.5, P = 0.003) and as a MRD (r = 0.4, P = 0.01) with favorable course. Kaplan-Meier curve for the presence of TEL-AML1 fusion at the diagnosis was associated with a better probability of overall survival (OS); mean survival time was 47 ± 1 month, in contrast to 28 ± 5 month in its absence (P = 0.006). Also, the persistence at TEL-AML1 fusion as a MRD was not significantly associated with a better probability of OS; the mean survival time was 42 ± 2 months in the presence of MRD and it was 40 ± 1 months in its absence. So, persistence of TEL-AML1 fusion as a MRD had no additive prognostic value over its measurement at diagnosis in terms of predicting the probability of OS.ConclusionFor most patients, the presence of TEL-AML1 fusion gene at diagnosis suggests a favorable prognosis. The present study suggests that persistence of TEL-AML1 fusion as MRD has no additive prognostic value.
Highlights
Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood
Patients were treated according to modified Berlin-Frankfurt-Munster (BFM-90) ALL protocol.21 t(12;21) was evaluated by fluorescence in situ hybridization (FISH) in newly diagnosed cases (80 patients) and after morphological remission in patients who were positive for t(12;21) as a minimal residual disease (MRD) (30 patients) and we determined the prognostic significance of TEL-AML1 fusion represented by disease course and survival and we clarified if the persistence of the TEL-AML1 fusion gene as MRD had an additive prognostic value
Five normal Bone marrow (BM) samples were taken as a control and the level of TEL-AML1 fusion by FISH estimated as 1 ± 0.2%
Summary
Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood. A recurrent t(12;21)(p13:q22) has been described in several human ALLs. A recurrent t(12;21)(p13:q22) has been described in several human ALLs In this translocation the TEL gene fuses to AML1; a gene previously cloned from translocation breakpoints in acute myeloid leukemia. These abnormalities consist of both translocations and deletions. All (95–100%) of TEL-AML1 positive ALL patients found to has a consistent cell surface immunophenotype. We raised a question if the opposite is true meaning that if CD 10 positive B-ALL immunophenotype will have a high incidence of positive TEL-AML1 fusion gene?. Can we use this fusion gene as a minimal residual disease (MRD) in this specific subgroup of B-ALL
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