Slower molecular response to treatment predicts poor outcome in patients with TEL/AML1 positive acute lymphoblastic leukemia: prospective real-time quantitative reverse transcriptase-polymerase chain reaction study
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
12491511
DOI
10.1002/cncr.11043
Knihovny.cz E-resources
- MeSH
- Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy metabolism MeSH
- Child MeSH
- DNA Primers chemistry MeSH
- Oncogene Proteins, Fusion genetics metabolism MeSH
- Infant MeSH
- Humans MeSH
- Chromosomes, Human, Pair 12 MeSH
- Chromosomes, Human, Pair 21 MeSH
- RNA, Messenger metabolism MeSH
- Adolescent MeSH
- Follow-Up Studies MeSH
- Infant, Newborn MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Child, Preschool MeSH
- Disease-Free Survival MeSH
- Prospective Studies MeSH
- Core Binding Factor Alpha 2 Subunit MeSH
- Antineoplastic Agents therapeutic use MeSH
- Neoplasm, Residual metabolism MeSH
- RNA, Neoplasm metabolism MeSH
- Translocation, Genetic MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DNA Primers MeSH
- Oncogene Proteins, Fusion MeSH
- RNA, Messenger MeSH
- Core Binding Factor Alpha 2 Subunit MeSH
- Antineoplastic Agents MeSH
- RNA, Neoplasm MeSH
- TEL-AML1 fusion protein MeSH Browser
BACKGROUND: The translocation t(12;21)(p13;q22), which produces the TEL/AML1 fusion gene, is the most frequent chromosomal abnormality in patients with childhood acute lymphoblastic leukemia (ALL) and generally is associated with a favorable prognosis. Furthermore, real-time quantitative-polymerase chain reaction (RQ-PCR)-based detection of TEL/AML1 represents an accurate technique for the reproducible assessment of minimal residual disease (MRD). METHODS: The authors employed RQ-reverse transcriptase-PCR (RQ-RT-PCR) technology to analyze MRD levels in 57 newly diagnosed patients with TEL/AML1 positive ALL in a prospective study. RESULTS: On Day + 33, a particularly important time point in terms of outcome prediction based on MRD monitoring, 75% of patients reached negativity, 13% of patients were positive at very low levels (< 10(-4); i.e., 1 or more leukemic cell per 10(4) normal cells), and another 13% of patients were positive at the level of 10(-2) to 10(-4) cells. No patient showed MRD levels > or = 10(-2) cells at this time. The data demonstrate that patients with TEL/AML1 positive ALL had a better response to induction chemotherapy on Day + 33 compared with a group of unselected patients with ALL (P = 0.0001). However, four patients with TEL/AML1 positive ALL developed relapse disease. Remarkably, these children were positive for MRD on Day + 33 at a level between 10(-2) cells and 10(-4) (n = 3 patients) and at < 10(-4) (n = 1 patient). Kaplan-Meier analysis of disease free survival showed the statistical significance of this distribution (MRD positive vs. MRD negative; log-rank P = 0.0016). CONCLUSIONS: The authors conclude that, although the TEL/AML1 positive leukemias generally are associated with a favorable outcome, MRD positivity assessed by RQ-RT-PCR analysis at the end of induction therapy represents a significantly negative prognostic feature.
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