Up-regulation of cell growth associated with an extra Y chromosome in a child with beta-thalassemia major having undergone hematopoietic stem cell transplant.
An extra Y chromosome(s) is occasionally found in patients with various hematologic neoplasias; however, an association with hereditary blood diseases is unknown. In a child with beta-thalassemia who received a transplant with sex-mismatched umbilical cord blood and neonatal blood, fluorescent in situ hybridization (FISH) with probes to X and Y chromosomes revealed an extra Y signal in 19.3% of the hepatocytes and in 38.9% of the pretransplant peripheral blood cells, yielding YY/Y ratios of 0.24 and 0.64, respectively. In granulocyte colony-stimulating factor-mobilized autologous peripheral blood stem cells, the FISH ratio of interphase XYY cells to XY cells was 1.64, and there were 3.4 times more G-banded XYY metaphases than normal metaphases. Both FISH and polymerase chain reaction persistently demonstrated posttransplant mixed chimerism. There was a greater proportion of residual autologous XYY cells than XY cells with a mean posttransplant YY/Y ratio of 1.56 (n = 13) (1 SD = 0.33; range, 1.10 to 2.17). In vitro clonogenic assays yielded a normal number of colony-forming units but no growth in cultures without growth factor supplement. This study suggests that hematopoietic stem cells with an extra Y chromosome may upregulate cell growth in response to cytokine stimulation. A posttransplant preponderance of XYY cells might be attributable to an extra Y chromosome in hematopoietic stem cells withstanding the myeloablative conditioning regimen.
Tsang
K S
KS
Department of Anatomical & Cellular Pathology, Chinese University of Hong Kong, Lady Pao's Children Cancer Centre, Prince of Wales Hospital, SAR.
Li
C K
CK
Chik
K W
KW
Wong
A P
AP
Lau
T T
TT
Li
K
K
Pong
H N
HN
Shing
M M
MM
Yuen
P M
PM
D002455:Cell Division; D002648:Child; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D009030:Mosaicism / Q000235:genetics; D014314:Trisomy; D015854:Up-Regulation; D014998:Y Chromosome; D017086:beta-Thalassemia / Q000235:genetics* / Q000473:pathology / Q000628:therapy