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Allelic loss of IRF1 in myelodysplasia and acute myeloid leukemia:
retention of IRF1 on the 5q- chromosome in some patients with the 5q-
syndrome
J Boultwood, C Fidler, S Lewis, A MacCarthy, H Sheridan, S Kelly, D Oscier, VJ Buckle and JS Wainscoat
Department of Haematology, John Radcliffe Hospital, Headington, Oxford,
United Kingdom.
Acquired interstitial deletions of the long arm of chromosome 5 occur
frequently in the myelodysplastic syndrome (MDS) and acute myeloid leukemia
(AML). Recently IRF1, a putative tumor suppressor gene localized to the
long arm of chromosome 5, has been shown to be deleted from the 5q-
chromosome in a group of patients with MDS and AML. It has been suggested
that the loss of IRF1 may be critical to the development of the 5q-
syndrome. We have investigated the allelic loss of IRF1 in a group of 12
patients with MDS and a 5q deletion and 2 patients with AML and a 5q
deletion. Gene dosage experiments demonstrated that 12 of 14 patients had
loss of one allele of the IRF1 gene but no evidence of homozygous loss and
that 2 patients with 5q- syndrome retained both copies of the gene. The
retention of IRF1 on the 5q- chromosome in these two cases has been
confirmed by fluorescent in situ hybridization localization using an IRF1
cosmid. Pulsed field gel electrophoresis was used to determine whether
there was any evidence for structural rearrangement in the region
encompassing the IRF1 gene in these two patients. No aberrant bands were
detected with a range of rare cutter enzyme digests. We conclude that IRF1
maps outside the commonly deleted segment of the 5q- chromosome and that
loss of IRF1 is not solely responsible for the development of the 5q-
syndrome.
Volume 82,
Issue 9,
pp. 2611-2616,
11/01/1993
Copyright © 1993 by The American Society of Hematology
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