Molecular genetic evidence of Y chromosome loss in male patients with hematological disorders.

BACKGROUND: There has been continuous debate as to whether Y chromosome loss is an age related phenomenon or a cytogenetic marker indicating a malignant change. This study aimed to investigate the frequency of Y chromosome loss in the specific patients in order to determine whether it is an age related phenomena or a cytogenetic marker indicating a malignant change.

METHODS: Five hundred and ninety-two male patients with a median age of 59 years old (22 - 95 years) were included in this study. These patients were divided into two groups: the study group, including 237 patients who had hematological disorders included myeloproliferative disorder (MPD), myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), multiple myeloma (MM), and lymphoma and the control group including 355 patients with no evidence of hematological disease. Both conventional cytogenetics and fluorescence in situ hybridization using DNA probes specific for the centromere of chromosomes X or Y were performed according to our standard laboratory protocols.

RESULTS: Twenty-four out of 237 patients with hematological disorders (10.1%) had Y chromosome loss. Of these 24 patients, 2 patients had AML (5.0% of all AML patients), 2 patients had CML (5.7% of all CML patients), 2 patients had MPD (8.0% of all MPD patients), 3 patients had MM (10.0% of all MM patients), 5 patients had lymphoma (10.6% of all lymphoma patients) and 10 patients had MDS (16.7% of all MDS patients). Twenty-one out of these 24 patients had a loss of Y chromosome as the sole anomaly and the remaining three had a loss of Y chromosome accompanied with other structural changes detected by conventional cytogenetic analysis. Fluorescence in situ hybridization (FISH) analysis confirmed the routine cytogenetic results. All 24 patients had a loss of Y chromosome with a range of 17.5% - 98.5% of cells. Two of the patients, one with AML and another with CML, had karyotype and FISH testing done both at the initial diagnosis and during remission. The results showed a loss of Y chromosome at initial diagnosis but a normal 46, XY karyotype during remission. Only 9 out of 355 patients (2.5%) without evidence of hematological disease had Y chromosome loss, among them 7 patients had cardiovascular diseases and 2 patients had kidney diseases. Comparison of the incidence of Y chromosome loss in patients with hematological disorders or without evidence of hematological disease using statistical analysis showed a statistically significance difference (P < 0.05).

CONCLUSIONS: The present study demonstrated that the frequency of Y chromosome loss is significantly higher in patients with hematological disorders than in patients without hematological disorders, which indicates that the loss of Y chromosome is associated with a neoplastic change.