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TEL gene is involved in myelodysplastic syndromes with either the typical
t(5;12)(q33;p13) translocation or its variant t(10;12)(q24;p13)
I Wlodarska, C Mecucci, P Marynen, C Guo, D Franckx, R La Starza, A Aventin, A Bosly, MF Martelli and JJ Cassiman
Center for Human Genetics, University of Leuven, Belgium.
A t(5;12)(q33;p13) translocation is a recurrent chromosome abnormality in a
subgroup of myeloid malignancies with features of both myeloproliferative
disorders and myelodysplastic syndromes (MDSs). The molecular consequence
of a t(5;12) is a fusion between the platelet- derived growth factor
receptor-B gene on chromosome 5 and a novel ETS- like gene, TEL, on
chromosome 12. We report on three patients with a t(5;12)(q33;p13)
diagnosed as chronic myelomonocytic leukemia, and one case of a
t(10;12)(q24;p13) in a progressive MDS, with eosinophilia and monocytosis.
Involvement of the TEL gene in these chromosome translocations was
investigated by fluorescence in situ hybridization (FISH) with cosmid
probes containing selectively the 5' end or 3' end of TEL. Hybridization of
these cosmids to the der(5)/der(10) or a der(12), respectively,
demonstrated a rearrangement of TEL in both translocations, showing that
the t(10;12) is a variant translocation of the t(5;12). Cloning of the
fusion cDNA of one case of t(5;12) showed that the breakpoint occurred at
the RNA level at exactly the same position as reported by Golub et al (Cell
77:307, 1994). In addition, the TEL gene on chromosome 12 could be
localized between two probes previously mapped to 12p13, namely PRB1 and
D12S178, leading to a better definition of the position of TEL in this
chromosome region. Moreover, in the case involving chromosome 10, the
breakpoint occurred between cKTN206 and cKTN312/LYT-10 at 10q24.
Clinicohematological data in these studies as well as the restriction
mapping of chromosomal breakpoints strongly suggest that (1) common
features in MDSs involving the TEL gene are monocytosis and eosinophilia,
(2) chromosomes other than no. 5 may be involved and at least a
t(10;12)(q24;p13) variant chromosome translocation does exist in these
MDSs, and (3) both standard and variant 12p/TEL translocations may be
identified by FISH with appropriate probes.
Volume 85,
Issue 10,
pp. 2848-2852,
05/15/1995
Copyright © 1995 by The American Society of Hematology
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