Clinical significance of Y chromosome loss in hematologic disease

✍ Scribed by Anne Wiktor; Benjamin A. Rybicki; Zhe Si Piao; Muhammad Shurafa; Bernd Barthel; Koichi Maeda; Daniel L. Van Dyke

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 82 KB
• Volume: 27
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/(sici)1098-2264(200001)27:1<11::aid-gcc2>3.0.co;2-i

✦ Synopsis

We have studied 215 male patients (aged 45-97 years) whose sole cytogenetic abnormality was clonal loss of the Y chromosome in metaphase cells from unstimulated cultures. The patients comprised a control group with no evidence of hematologic disease and four disease case groups: 1) myelodysplastic syndrome (MDS), refractory anemia, refractory anemia with excess blasts (RAEB), RAEB in transformation, and chronic myelomonocytic leukemia; 2) acute myelogenous leukemia; 3) myeloproliferative disorder (MPD), chronic granulocytic leukemia, and polycythemia vera; and 4) B-cell lymphoma/leukemia. The frequency of cells with Y loss increased with age and was significantly greater in cases than in controls, but it was not correlated with survival or with prior therapy. The frequency of cases with a -Y clone was 6.3% of male karyotypes and represented 16.4% of all abnormal male cytogenetic reports. Much of the difference between cases and controls appears to be accounted for by a greater frequency of cases with Ͼ 75% Y loss. A value of 81% chromosome Y loss maximized the combined sensitivity (28%) and specificity (100%) for predicting disease status, but a 75% cutoff provided the best estimate of disease risk. Even in older males, if Ͼ 75% of metaphase cells are 45,X,-Y, they probably represent a disease-associated clonal population, and it is possible that the critical genetic change is not visible through the microscope. This observation is true for MDS, MPD, B-cell disease, and especially acute myelogenous leukemia. The prognostic association of Y chromosome loss for survival appears to be neutral or favorable.