title: Origins of "late" relapse in childhood acute lymphoblastic leukemia with TEL-AML1 fusion genes.
abstract: Approximately 20% of childhood B-precursor acute lymphoblastic leukemia (ALL) has a TEL-AML1 fusion gene, often in association with deletions of the nonrearranged TEL allele. TEL-AML1 gene fusion appears to be an initiating event and usually occurs before birth, in utero. This subgroup of ALL generally presents with low- or medium-risk features and overall has a very good prognosis. Some patients, however, do have relapses late or after the cessation of treatment, at least on some therapeutic protocols. They usually achieve sustained second remissions. Posttreatment relapses, or even very late relapses (5-20 years after diagnosis), in childhood ALL are clonally related to the leukemic cells at diagnosis (by IGH or T-cell receptor [TCR] gene sequencing) and are considered, therefore, to represent a slow re-emergence or escape of the initial clone seen at diagnosis. Microsatellite markers and fluorescence in situ hybridization identified deletions of the unrearranged TEL allele and IGH/TCR gene rearrangements were analyzed; the results show that posttreatment relapse cells in 2 patients with TEL-AML1-positive ALL were not derived from the dominant clone present at diagnosis but were from a sibling clone. In contrast, a patient who had a relapse while on treatment with TEL-AML1 fusion had essentially the same TEL deletion, though with evidence for microsatellite instability 5(') of TEL gene deletion at diagnosis, leading to extended 5(') deletion at relapse. It is speculated that, in some patients, combination chemotherapy for childhood ALL may fail to eliminate a fetal preleukemic clone with TEL-AML1 and that a second, independent transformation event within this clone after treatment gives rise to a new leukemia masquerading as relapse. (Blood. 2001;98:558-564)
authors.affiliation: Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom.
authors.forename: A M
authors.initials: AM
authors.lastname: Ford
authors.forename: K
authors.initials: K
authors.lastname: Fasching
authors.forename: E R
authors.initials: ER
authors.lastname: Panzer-Grümayer
authors.forename: M
authors.initials: M
authors.lastname: Koenig
authors.forename: O A
authors.initials: OA
authors.lastname: Haas
authors.forename: M F
authors.initials: MF
authors.lastname: Greaves
mesh_terms: D002675:Child, Preschool; D002999:Clone Cells / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D015329:Gene Rearrangement, T-Lymphocyte; D019672:Genes, T-Cell Receptor; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D018895:Microsatellite Repeats; D016609:Neoplasms, Second Primary / Q000209:etiology* / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D011505:Protein-Tyrosine Kinases; D050783:Proto-Oncogene Proteins c-ets; D012008:Recurrence; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein; C426234:TEL-ABL fusion protein, human