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Pre-clinical evaluation of probes to detect t(8;21) AML minimal residual disease by fluorescence in situ hybridization.
- Source :
-
Genes, chromosomes & cancer [Genes Chromosomes Cancer] 1998 Feb; Vol. 21 (2), pp. 144-51. - Publication Year :
- 1998
-
Abstract
- The 8;21 translocation in acute myeloid leukemia (AML) results in a consistent fusion transcript, AML1/ETO. Long-term clinical remission occurs in some patients despite incomplete eradication of AML1/ETO as demonstrated by RT-PCR, thus limiting the usefulness of this assay. An important future goal will be to determine if there is a level of minimal residual disease (MRD) in patients below which relapse is unlikely. For the detection of MRD, we have developed reagents for fluorescence in situ hybridization (FISH) that identify both derivative 8 and 21 chromosomes with a high analytical sensitivity. In t(8;21) AML cells, two fused signals were detected in addition to the normal 8 and 21 alleles. The sensitivity and specificity of this probe mixture were analyzed in cell lines and patient bone marrows. One and two randomly juxtaposed signals were observed in 2.4 and 0.04% of normal cells, respectively. However, these were easily differentiated from t(8;21) cells by the absence of signals from the normal alleles. Using as criteria the presence of two fused signals plus the normal alleles, we observed no false positives among 5,000 normal cells. The probe correctly identified 20/20 patients with t(8;21) AML and 10/10 non-t(8;21) patients. In cell dilution experiments, the analytical sensitivity of this reagent was equal to that of the X chromosome and Y chromosome alpha-satellite probes. These optimized probes should facilitate the quantitative assessment and study of MRD in t(8;21) AML.
- Subjects :
- Bone Marrow Cells pathology
Chromosome Mapping
Core Binding Factor Alpha 2 Subunit
Humans
In Situ Hybridization, Fluorescence
Leukemia, Myeloid, Acute diagnosis
Neoplasm, Residual diagnosis
RUNX1 Translocation Partner 1 Protein
Recombinant Fusion Proteins analysis
Recombinant Fusion Proteins genetics
Sensitivity and Specificity
Transcription Factors analysis
Transcription Factors genetics
Chromosomes, Human, Pair 21 genetics
Chromosomes, Human, Pair 8 genetics
DNA Probes
Fluorescent Dyes
Leukemia, Myeloid, Acute genetics
Neoplasm, Residual genetics
Oncogene Proteins, Fusion
Translocation, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 1045-2257
- Volume :
- 21
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Genes, chromosomes & cancer
- Publication Type :
- Academic Journal
- Accession number :
- 9491326