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Genes Chromosomes Cancer. 2015 Dec;54(12):717-24. doi: 10.1002/gcc.22282. Epub 2015 Sep 23.

New data shed light on Y-loss-related pathogenesis in myelodysplastic syndromes.

Author information

1
Department of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany.
2
Praxis für Hämatologie und Onkologie, Lüdenscheid, Germany.
3
Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany.
4
1st Medical Department with Hematology, Stem Cell Transplantation, Hemostasis and Medical Oncology, Elisabethinen Hospital, Linz, Austria.
5
Red Cross Blood Transfusion Service of Upper Austria, Austrian Cluster for Tissue Regeneration, Linz, Austria.
6
Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany.
7
Department of Transfusion Medicine, University Medical Center Göttingen, Göttingen, Germany.

Abstract

Loss of the Y-chromosome (LOY) is described as both a normal age-related event and a marker of a neoplastic clone in hematologic diseases. To assess the significance of LOY in myelodysplastic syndromes (MDS), we determined the percentage of LOY in clonal CD34+ peripheral blood cells in comparison to normal CD3+ T-cells of 27 MDS patients using fluorescence in situ hybridization (FISH) analysis. Results were compared with the percentage of LOY in CD34+ and CD3+ cells of 32 elderly men without hematologic diseases and in 25 young blood donors. While LOY could not be detected in CD3+ cells of young men, it was observed in CD3+ cells of elderly men without hematologic diseases (2.5% LOY) as well as in CD3+ cells of elderly MDS patients (5.8% LOY). The percentage of CD34+ cells affected by LOY was significantly higher in MDS patients compared to elderly men without hematologic diseases (43.3% vs. 13.2%, P = 0.005), indicating that LOY has an age-related basis but is also associated with MDS. Furthermore, we aimed to define a threshold between age- and disease-associated LOY in MDS. Statistical analysis revealed that a value of 21.5% LOY in CD34+ peripheral blood cells provided the best threshold to discriminate between these two conditions in MDS. We conclude that LOY is clonal in a substantial number of MDS based on an age-related predisposition.

PMID:
26394808
DOI:
10.1002/gcc.22282
[Indexed for MEDLINE]

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