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Is TEL/AML1 fusion gene appropriate marker for minimal residual disease monitoringin children with acute lymphoblastic leukaemia?


Authors: J. Madžo 1,2;  K. Mužíková 1;  E. Froňková 1;  L. Šrámková 1;  L. Zemanová 1;  J. Zuna 1;  J. Starý 3;  J. Trka 1,*
Authors‘ workplace: CLIP – Childhood Leukaemia Investigation Prague, Klinika dětské hematologie a onkologie, 2 Ústav fyziologie, UK 2. LF, Praha, 3 Klinika dětské hematologie a onkologie, UK 2. LF a FN v Motole, Praha, * korespondující autor 1
Published in: Transfuze Hematol. dnes,, 2004, No. 4, p. 137-142.
Category:

Overview

Currently the quantitative detection of clonal-specific rearrangements of immunoreceptor genes (T-cellreceptors and immunoglobulins) is considered to be the standard approach in minimal residual disease(MRD) monitoring in childhood acute lymphoblastic leukaemia. However, optimisation of two independentrearrangements with sensitivity of at least one malignant cell among 10 000 normal cells is notsuccessful in all patients. TEL/AML1 fusion gene is the most common chromosomal aberration inchildhood acute lymphoblastic leukaemia and is present in more than 20% of patients. Comparison ofresidual disease levels examined simultaneously by quantitative polymerase chain reaction onTEL/AML1 transcript and on immunoreceptor gene rearrangements in 41 samples showed very goodoverall correlation with only two exceptions (R2=0,847). Thus, quantitative detection of TEL/AML1transcript can serve as an alternative target for MRD monitoring in patients with TEL/AML1-positiveleukaemia and a lack of sensitive standard markers – immunoreceptor gene rearrangements. Among52 patients with residual disease level tested at the end of induction therapy, the presence ofTEL/AML1-positive cells reliably separated patients with poor prognosis (relapse free survival = 50%, 7 relapses in14 patients) from children with excellent outcome (relapse free survival = 92%, 3 relapses in 38 patients,p=0,0007). Detectable TEL/AML1-positive cells at the end of induction therapy thus predict relapse witha high probability even though the relapse occurs 57 months from the original diagnosis.

Key words:
childhood acute lymphoblastic leukemia, TEL/AML1, quantitative PCR, minimal residualdisease

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Haematology Internal medicine Clinical oncology
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