Publication Date:
2008-11-16
Description:
Approximately 20–25% of children with B-cell precursor ALL harbour the t(12;21) (p13;q22)/ETV6-RUNX1 fusion which has been associated, almost universally, with a favourable outcome. However, as some ETV6-RUNX1 patients relapse additional predictors of treatment failure are required. Although additional abnormalities involving 12p and 21q (AA) are known to occur in these patients, previous studies have produced conflicting results with respect to their prognostic impact. In order to investigate the prognostic relevance of AA in this subset of patients, we screened a large cohort of children by FISH with break-apart probes targeting the ETV6 (DakoCytomation, Denmark) and RUNX1 loci (centromeric - RP11-272A03 and telomeric - RP11-396G11, Sanger Institute, UK). Among 368 ETV6-RUNX1 patients treated on the MRC ALL97 childhood treatment trial, material was available for testing on 247 (67%). Sample availability was not related to sex or age, but those tested were more likely to have a white cell count (WCC) of 〉50×109/L and hence had a borderline inferior event free survival (EFS) at 5 years: 86% (SE 2.2%) v 93% (2.4%), p=0.05. FISH testing with the ETV6 and RUNX1 probes was successful in 245 (99%) and 244 (99%) patients, respectively. In total, 202 (82%) patients harboured at least one of the following five AA: loss of the untranslocated ETV6 allele (ETV6del): 165 (67%); Gain of a normal chromosome 21 (+21): 57 (23%); Gain of a der(21)t(12;21) chromosome [+der(21)]: 38 (16%); deletions from the der(12)t(12;21) [der(12)del]: 20 (8%) and gain of the der(12) t(12;21) [+der(12)]: 18 (7%). In 74 (30%) cases two or more of these AA were observed. Evidence that the ETV6-RUNX1 clone had doubled to a near-tetraploid clone was seen in 9 (4%) cases. In the majority of ETV6del cases (158, 96%) the deletion resulted in the loss of the entire ETV6 probe which spanned a region of ~750kb. The proportion of ETV6-RUNX1 positive cells carrying each specific AA ranged from 6% to 100% but in the majority of cases comprised more than 75% cells: 72%, 54%, 63%, 100% and 39%, respectively. The frequency of the AA did not vary by sex, with the exception of +der(12) which was more common among females (12%) than males (4%) [p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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