Open AccessQuantitative monitoring of minimal residual disease in childhood acute lymphoblastic leukemia using TEL ‐ AML 1 fusion transcript as a marker
Author(s) -
Zhao Xiaoxi,
Gao Chao,
Cui Lei,
Li Weijing,
Liu Shuguang,
Zhang Ruidong,
Liu Yi,
Wu Minyuan,
Li Zhigang
Publication year - 2018
Publication title -
pediatric investigation
Language(s) - English
Resource type - Journals
ISSN - 2574-2272
DOI - 10.1002/ped4.12098
Subject(s) - minimal residual disease , medicine , spearman's rank correlation coefficient , t cell receptor , lymphoblastic leukemia , rank correlation , fusion gene , oncology , real time polymerase chain reaction , risk stratification , gene rearrangement , gastroenterology , leukemia , immunology , biology , gene , t cell , genetics , mathematics , statistics , immune system
Importance By demonstrating with TEL ‐ AML 1 , this study indicated that mRNA s 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 ‐ AML 1 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 ‐ AML 1 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 ‐ AML 1 level was analyzed at each time point. The correlation between the MRD levels determined by TEL ‐ AML 1 or Ig/ TCR rearrangements was also analyzed. Results For day 33, 6.68 TEL ‐ AML 1 copies/10 4 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/10 4 ABL copies respectively; patients with higher expression levels had lower RFS s (day 15: P = 0.027; month 3: P = 0.023). For days 15 and 33, MRD levels assessed using TEL ‐ AML 1 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 ‐ AML 1 was a better prognostic marker. Interpretation TEL ‐ AML 1 is an effective marker for MRD assessment and relapse prediction in children with ALL .