title: TEL-AML1 fusion RNA as a new target to detect minimal residual disease in pediatric B-cell precursor acute lymphoblastic leukemia.
abstract: It has recently been shown that the t(12;21)(p13;q22) translocation fuses two genes, TEL on chromosome 12 and AML1 on chromosome 21. We have evaluated the frequency of this newly described translocation in acute lymphoblastic leukemia (ALL), and the feasibility of minimal residual disease (MRD) monitoring by polymerase chain reaction (PCR) amplification of TEL-AML1 transcripts. Thirty-nine adult- and 45 childhood-ALLs consecutively diagnosed in a single center were included in this study. TEL-AML1 fusion transcripts were searched for in the 39 adult- and 45 childhood-ALLs for which material was available. BCR-ABL, E2A-PBX1, and MLL-AF4 transcripts were also studied by PCR in these cases. TEL-AML1 transcripts were found in 8 out of 35 (23%) childhood B-cell precursor ALLs (BCP-ALLs). TEL-AML1 transcripts were detected in only 1 of 31 adult BCP-ALLs (P = .04, Fisher's exact test). Nevertheless, in this adult case, TEL-AML1 transcripts were found at a low level in 2 of 3 different samples. BCR-ABL, E2A-PBX1, and MLL-AF4 transcripts were found in 12, 3, and 1 cases of 31 adult BCP-ALLs, and in 1, 2, and 1 cases of 35 childhood BCP-ALLs, respectively. TEL-AML1 transcripts were never found associated with any other fusion transcripts. Taken together, the four types of chimeric transcripts were detected in 12 of 35 (34%) childhood BCP-ALL cases. No TEL-AML1 transcripts were detected in 11 T-cell ALLs (4 adults and 5 children), nor in 2 B-cell (slg+) ALLs. MRD was evaluated in 21 samples collected in 9 TEL-AML1+ childhood BCP-ALL cases during therapy (median follow-up = 200 days). Of 8 patients evaluated after induction therapy, 4 showed detectable but low levels of MRD. Of 7 patients serially evaluated, only one showed persistence of detectable MRD. This study shows that TEL-AML1 transcripts are frequently detected in pediatric BCP-ALLs and that these transcripts are molecular targets that will simplify the strategy of MRD monitoring in childhood BCP-ALL.
authors.affiliation: Department of Clinical Hematology, Hôpital Saint-Louis, Paris, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Cayuela
authors.forename: A
authors.initials: A
authors.lastname: Baruchel
authors.forename: C
authors.initials: C
authors.lastname: Orange
authors.forename: A
authors.initials: A
authors.lastname: Madani
authors.forename: M F
authors.initials: MF
authors.lastname: Auclerc
authors.forename: M T
authors.initials: MT
authors.lastname: Daniel
authors.forename: G
authors.initials: G
authors.lastname: Schaison
authors.forename: F
authors.initials: F
authors.lastname: Sigaux
mesh_terms: D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit; D003348:Cortisone / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000235:genetics*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000032:analysis*; D012334:RNA, Neoplasm / Q000032:analysis*; D012097:Repressor Proteins; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D014750:Vincristine / Q000008:administration & dosage; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D018943:Anthracyclines; D001215:Asparaginase; D014408:Biomarkers, Tumor; D050676:Core Binding Factor Alpha 2 Subunit; D003348:Cortisone; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012097:Repressor Proteins; D014157:Transcription Factors; D014750:Vincristine; D000097764:ETS Translocation Variant 6 Protein; C493728:RUNX1 protein, human