Non-random involvement of chromosome 13 in patients with persistent or relapsed disease after bone-marrow transplantation for chronic myeloid leukemia.
Chronic myeloid leukemia (CML) patients with persistent or relapsed disease following bone-marrow transplantation (BMT) usually show both clonal and non-clonal cytogenetic changes in addition to the Philadelphia (Ph) translocation. These changes are presumably due to conditioning prior to transplantation and are generally not thought to be of clinical significance. We have examined the additional cytogenetic changes found in Ph+ve cells after BMT in 47 CML patients. Forty patients showed clonal changes. The involvement of each chromosome was compared statistically with expected values assuming that further chromosome changes are random and related to chromosome size. In clones that comprised 50% or more of the Ph+ve metaphases, chromosome 13 was involved in 12 of 22 clones (55%); this was highly significant when compared with the theoretical expected value of 3.2 (14.5%) (P < 0.001). The chromosome 13 rearrangements comprised both translocations and deletions. By means of FISH with a panel of 13q YAC clones, the breakpoints in 6 of these patients were investigated, but no common site of translocation was identified. The YAC panel was then used on material from 6 patients with chromosomal deletions. A common region of deletion was identified at 13q12-14, suggesting the presence of one or more tumor suppressor genes. We conclude that chromosome 13 deletions are non-randomly overrepresented in Ph+ve metaphases following BMT for CML. Genes Chromosomes Cancer 27:278-284, 2000.
Chase
A
A
Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom. achase@ic.ac.uk
Pickard
J
J
Szydlo
R
R
Coulthard
S
S
Goldman
J M
JM
Cross
N C
NC
D016026:Bone Marrow Transplantation; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D002999:Clone Cells; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D008297:Male; D012008:Recurrence; D014178:Translocation, Genetic / Q000235:genetics