Molecular characterization of the recurrent unbalanced translocation der(1;7)(q10;p10)

Abstract

An unbalanced translocation der(1;7)(q10; p10) is a nonrandom chromosomal aberration commonly observed in myelodysplastic syndrome and acute myeloid leukemia. We molecularly analyzed the breakpoints of der(1;7)(q10;p10) by quantitative fluorescent in situ hybridization (FISH) analyses using centromeric satellite DNAs mapped to chromosomes 1 and 7 as probes. We found that the signal intensities of 2 centromere alphoid probes, D1Z7 on chromosome 1 and D7Z1 on chromosome 7, were almost invariably reduced on the derivative chromosome compared with those on their normal counterparts. These results suggest that this translocation results from the recombination between the 2 alphoids, which was further confirmed by fiber FISH experiments. Because the relative reduction in the intensities of D1Z7 and D7Z1 signals on the derivative chromosomes was highly variable among patients, it was estimated that the breakpoints in these patients were randomly distributed over several megabase pairs within each alphoid cluster except for its extreme end to the short arm. Our results provide a novel insight into the structural basis for generation of this translocation as well as its leukemogenic roles. (Blood. 2003;102: 2597-2604)

Clinical and cytogenetic features of 508 Chinese patients with myelodysplastic syndrome and comparison with those in Western countries

“…The t(3;5)(q25;q34) translocation, seen in one of our patients, rearranges NPM gene with MLF1 gene and related to MDS progression to AML. 22 Translocations involving chromosome 1 were also observed in two cases of der(1;7)(q10;p10), as previously reported in MDS, 23 and in one case with t(1;2)(q21;q37) in our series, in which we identified a new HHL (human hornerin like) gene on 1q21 and showed that its overexpression might be related to MDS/AML transformation (manuscript prepared by YY Wang, SJ Chen et al).…”

Mosaicism due to myeloid lineage–restricted loss of heterozygosity as cause of spontaneous Rh phenotype splitting

“…Together with the 2 1p and 3 1q subtelomere signals (data not shown), this FISH pattern defines a der(1,7)(q10;p10), a nonrandom chromosome rearrangement that is highly specific for a particular subset of neoplastic myeloid disorders. 41,42 Although these findings corroborate a potential biologic link between the phenomenon described herein and the recently documented acquired partial uniparental disomies in AML, the small homozygous stretch surrounding the RHD/ RHCE gene region in this instance also implied that its underlying somatic recombination event was not directly linked with the one generating the chromosomal abnormality. 41,43,44 Rh antigen and Rh complex molecule expression levels of D-negative red cell subpopulations reflect the mechanisms of loss of heterozygosity…”

Therapy-related acute myeloid leukemia after single-agent treatment with fludarabine for chronic lymphocytic leukemia

“…The leukemia was characteristic of t-AML in showing trilineage myelodysplastic features. Furthermore, the unbalanced translocation der(1;7)(q10;p10), resulting effectively in monosomy 7q (7qÀ), was also typically found in t-AML/MDS [7]. Therefore, according to the current World Health Organization classification scheme, the leukemia was classified as t-AML.…”