Ford, A. M., Fasching, K., Panzer-Grumayer, E. R., Koenig, M., Haas, O. A., Greaves, M. F. (2001) Origins of "late" relapse in childhood acute lymphoblastic leukemia with TEL-AML1 fusion genes. BLOOD, 98 (3). pp. 558-564. ISSN 0006-4971

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Abstract

Origins of "late" relapse in childhood acute lymphoblastic leukemia with TEL-AML1 fusion genes Approximately 20% of childhood B-precursor acute lymphoblastic leukemia (ALL) has a TEL-AML I 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-AML 1 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 fall to eliminate a fetal preleukemic clone with TEL-AML I and that a second, Independent transformation event within this clone after treatment gives rise to a new leukemia masquerading as relapse.

Item Type:	Article
Authors (ICR Faculty only):	Greaves, Mel and Ford, Tony
All Authors:	Ford, A. M., Fasching, K., Panzer-Grumayer, E. R., Koenig, M., Haas, O. A., Greaves, M. F.
Uncontrolled Keywords:	ACUTE MYELOGENOUS LEUKEMIA; PEDIATRIC-ONCOLOGY-GROUP; TEL/AML1 FUSION; BONE-MARROW; EXCELLENT PROGNOSIS; CHROMOSOME 12P12.3; CLONAL STABILITY; IDENTICAL-TWINS; CHILDREN; TRANSCRIPT
Research teams:	ICR divisions > Molecular Pathology > Biology of Childhood Leukaemia
Depositing User:	EPrints Services
Date Deposited:	10 Aug 2007 20:38
Last Modified:	10 Feb 2010 11:44
URI:	http://publications.icr.ac.uk/id/eprint/669

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