TY - JOUR
T1 - Clinical significance of Y chromosome loss in hematologic disease
AU - Wiktor, Anne
AU - Rybicki, Benjamin A.
AU - Piao, Zhe Si
AU - Shurafa, Muhammad
AU - Barthel, Bernd
AU - Maeda, Koichi
AU - Van Dyke, Daniel L.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2000/1
Y1 - 2000/1
N2 - 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 > 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 > 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.
AB - 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 > 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 > 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.
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U2 - 10.1002/(SICI)1098-2264(200001)27:1<11::AID-GCC2>3.0.CO;2-I
DO - 10.1002/(SICI)1098-2264(200001)27:1<11::AID-GCC2>3.0.CO;2-I
M3 - Article
C2 - 10564581
AN - SCOPUS:0033991486
SN - 1045-2257
VL - 27
SP - 11
EP - 16
JO - Genes Chromosomes and Cancer
JF - Genes Chromosomes and Cancer
IS - 1
ER -