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Consistent loss of the D5S89 locus mapping telomeric to the interleukin
gene cluster and centromeric to EGR-1 in patients with 5q- chromosome
L Nagarajan, J Zavadil, D Claxton, X Lu, J Fairman, JA Warrington, JJ Wasmuth, AC Chinault, CE Sever and ML Slovak
Department of Hematology, University of Texas M.D. Anderson Cancer Center,
Houston 77030.
Interstitial deletions of the long arm of chromosome 5 are common in a
number of disorders of leukemic and preleukemic myeloid disorders. Although
the limits of these deletions vary among patients, a region of cytogenetic
overlap that includes band 5q31 is deleted consistently, suggesting loss of
5q31 loci critical for normal myeloid differentiation and leukemogenesis.
An anonymous genomic DNA segment D5S89, previously mapped to 5q21-31,
detects consistent loss of alleles in cases showing the 5q- chromosome at
presentation or relapse. Analysis of a panel of natural-deletion
somatic-cell hybrids in conjunction with irradiation hybrids containing
fragments of human chromosome 5q shows that the D5S89 locus is telomeric to
the interleukin (IL) genes (IL-3, IL-4, IL-5, IL-9, and granulocyte-
macrophage colony-stimulating factor [GM-CSF]) and interferon response
factor-1 (IRF-1) gene and centromeric to the early response transcription
factor (early growth response gene-1 [EGR-1]) on 5q31. To further define
the principal region of loss, we have isolated and characterized yeast
artificial chromosomes (YACs) spanning D5S89. The presence of several CpG
islands within the 300-kb YAC is suggestive of multiple transcription
units. However, IL-4, IL-5, IRF-1, IL-3, GM-CSF, and EGR-1 genes were not
detected in the YAC clone spanning D5S89, implying that none of these genes
are in the vicinity of the D5S89 marker. Further characterization of these
YACs should facilitate the isolation of novel candidate genes that may play
a role in the evolution of the abnormal phenotype associated with 5q-
chromosome.
Volume 83,
Issue 1,
pp. 199-208,
01/01/1994
Copyright © 1994 by The American Society of Hematology
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