title: Clinical significance of Y chromosome loss in hematologic disease.
abstract: 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. Genes Chromosomes Cancer 27:11-16, 2000.
authors.affiliation: Department of Medical Genetics, Josephine Ford Cancer Center, Henry Ford Health System, Detroit, MI 48202, USA.
authors.forename: A
authors.initials: A
authors.lastname: Wiktor
authors.forename: B A
authors.initials: BA
authors.lastname: Rybicki
authors.forename: Z S
authors.initials: ZS
authors.lastname: Piao
authors.forename: M
authors.initials: M
authors.lastname: Shurafa
authors.forename: B
authors.initials: B
authors.lastname: Barthel
authors.forename: K
authors.initials: K
authors.lastname: Maeda
authors.forename: D L
authors.initials: DL
authors.lastname: Van Dyke
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics; D000782:Aneuploidy; D002872:Chromosome Deletion; D006402:Hematologic Diseases / Q000175:diagnosis / Q000235:genetics*; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013997:Time Factors; D014998:Y Chromosome / Q000235:genetics*