Quantitative monitoring of minimal residual disease in childhood acute lymphoblastic leukemia using TEL-AML1 fusion
Xiaoxi Zhao1, Chao Gao1, Lei Cui2
1Beijing Key Laboratory of Pediatric Hematology Oncology National Key Discipline of Pediatrics (Capital Medical University) Key Laboratory of Major Diseases in Children Ministry of Education Hematology Oncology Center Beijing Children's Hospital Capital Medical University National Center for Children's Health Beijing China.
Importance:
By demonstrating with TEL-AML1, this study indicated that mRNAs transcribed from fusion genes are ideal targets for minimal residual disease (MRD) monitoring in childhood acute lymphoblastic leukemia, and that different thresholds are needed to apply them into the risk stratification.
Objective:
TEL-AML1 expression was measured at three time points to 1) determine cut-off values for predicting acute lymphoblastic leukemia (ALL) relapse; 2) investigate the prognostic value of this method and how well the results at these time points correlated; 3) determine the correlation between MRD levels assessed using this marker and that determined by immunoglobulin/T-cell receptor (Ig/TCR) rearrangement detection.
Methods:
TEL- AML1 expression in 62 children with ALL was quantitated by real-time quantitative PCR at day 15, day 33, and month 3. The relationship between patient outcome and TEL-AML1 level was analyzed at each time point. The correlation between the MRD levels determined by TEL-AML1 or Ig/TCR rearrangements was also analyzed.
Results:
For day 33, 6.68 TEL-AML1 copies/104 ABL copies was determined to be the best cut-off value. Higher levels were correlated with relapse (P = 0.001). For day 15 and month 3, the best cut-off values were 336.5 and 0.85 copies/104 ABL copies respectively; patients with higher expression levels had lower RFSs (day 15: P = 0.027; month 3: P = 0.023). For days 15 and 33, MRD levels assessed using TEL-AML1 or Ig/TCR rearrangements were strongly correlated [Spearman rank correlation coefficient (ρ) = 0.729 (day 15), 0.719 (day 33); P < 0.001 (both)], and both methods were equally effective at predicting relapse. At month 3, there was moderate correlation between the results derived from the two markers (ρ = 0.418, P = 0.003); however, receiver operating characteristic curve analysis showed that TEL-AML1 was a better prognostic marker.
Interpretation:
TEL-AML1 is an effective marker for MRD assessment and relapse prediction in children with ALL.
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