| Disease | -Y is frenquently observed in myeloproliferative diseases (MPD), myelodysplasic syndromes (MDS), acute non lymphocytic leukemias (ANLL), and can also be seen in lymphoproliferations |
| Epidemiology | In CML with t(9;22) and in ANLL with a t(8;21), loss of the Y chromosome tends to occurs at a younger age than in the general population |
| Clinics | Partial or complete reappearance of the Y chromosome has been described in several cases of ANLL in remission. In most or all of these ANLL cases, the 45,X,-Y cell population represented 80-100% of pre-remission metaphases. These observations support the interpretation that the leukemia cell karyotype is 45,X,-Y. In MDS, the proportion of -Y cells has been observed to increase, decrease, remain stable, or fluctuate up and down on follow-up studies. In four cases of Hodgkin disease, simultaneous fluorescence immunophenotyping and FISH showed that the -Y cell population was probably independent of the Hodgkin disease in at least two of the patients. It is notable that the -Y cells represented fewer than 10-15% of the metaphase cells in all four cases. |
| Cytology | no known association |
| Prognosis | In ANLL, a 45,X,-Y karyotype is believed to have an intermediate prognosis. In MDS, the prognosis appears to be neutral or favorable. There are insufficient data for MPD or lymphoproliferative disease |
| Cytogenetics Morphological | In PHA-stimulated lymphocyte karyotype studies of males, about 2% have one or more cells with loss of the Y chromosome. Cells with -Y are observed more often in males over age 55 than in younger males. In all age groups, the proportion of -Y cells is usually under 10%. The pattern of Y loss is more striking in bone marrow aspirate karyotype studies. Here, clonal Y chromosome loss as a sole abnormality in the karyotype is a common finding. A 45,X,-Y karyotype is observed in about 6% of bone marrow karyotype studies from males, and it represents 15-20% of abnormal karyotypes. The frequency of -Y cells increases with advancing age and is significantly greater in cases with MDS, MPD, ANLL, or lymphoproliferative disease than in subjects who have no evidence of disease. Subjects with no evidence of disease rarely exhibit more than 75% of cells with 45,X,-Y. Thus, if fewer than 75% of metaphase cells are -Y, the disease association is uncertain. However, if 75-100% of metaphase cells are -Y, the karyotype probably is disease-associated, even in older men. Chromosome rearrangements involving the Y chromosome are rare in cancer and leukemia. Loss of the Y chromosome, in contrast, is a common secondary change in cancer cells and in a few leukemias (see below). |
| Additional anomalies | In association with t(9;22) in CML and with t(8;21) in FAB-M2 ANLL, loss of the Y chromosome is generally considered a secondary event of no added clinical significance. |
| Age-associated aneuploidy: loss of Y chromosome from human bone marrow cells with aging. |
| Pierre RV, Hoagland HC |
| Cancer. 1972 ; 30 (4) : 889-894. |
| PMID 4116908 |
| |
| Y chromosome loss in leukemias. |
| Berger R, Bernheim A |
| Cancer Genet Cytogenet. 1979 ; 1 : 1-8. |
| |
| Chromosomes and causation of human cancer and leukemia. XXXV. The missing Y in acute non-lymphocytic leukemia (ANLL). |
| Abe S, Golomb HM, Rowley JD, Mitelman F, Sandberg AA |
| Cancer. 1980 ; 45 (1) : 84-90. |
| PMID 6985828 |
| |
| Loss of the Y chromosome in acute myelogenous leukemia: a report of 13 patients. |
| Holmes RI, Keating MJ, Cork A, Trujillo JM, McCredie KB, Freireich EJ |
| Cancer genetics and cytogenetics. 1985 ; 17 (3) : 269-278. |
| PMID 3859363 |
| |
| Acute myelogenous leukemia with an 8;21 translocation. A report on 148 cases from the Groupe Franˆßais de Cytogˆ©nˆ©tique Hˆ©matologique. |
| Cancer genetics and cytogenetics. 1990 ; 44 (2) : 169-179. |
| PMID 2297675 |
| |
| The frequency of aneuploidy in cultured lymphocytes is correlated with age and gender but not with reproductive history. |
| Nowinski GP, Van Dyke DL, Tilley BC, Jacobsen G, Babu VR, Worsham MJ, Wilson GN, Weiss L |
| American journal of human genetics. 1990 ; 46 (6) : 1101-1111. |
| PMID 2339703 |
| |
| Loss of the Y chromosome from normal and neoplastic bone marrows. United Kingdom Cancer Cytogenetics Group (UKCCG) |
| Genes, chromosomes & cancer. 1992 ; 5 (1) : 83-88. |
| PMID 1384666 |
| |
| X and Y chromosome loss as sole abnormality in acute non-lymphocytic leukemia (ANLL) |
| Riske CB, Morgan R, Ondreyco S, Sandberg AA |
| Cancer genetics and cytogenetics. 1994 ; 72 (1) : 44-47. |
| PMID 8111738 |
| |
| Y chromosome loss in chronic myeloid leukemia detected in both normal and malignant cells by interphase fluorescence in situ hybridization. |
| Kirk JA, VanDevanter DR, Biberman J, Bryant EM |
| Genes, chromosomes & cancer. 1994 ; 11 (3) : 141-145. |
| PMID 7530482 |
| |
| Loss of Y chromosome. An age-related event or a cytogenetic marker of a malignant clone? |
| Abeliovich D, Yehuda O, Ben-Neriah S, Or R |
| Cancer genetics and cytogenetics. 1994 ; 76 (1) : 70-71. |
| PMID 8076356 |
| |
| Clarification of dubious karyotypes in Hodgkin's disease by simultaneous fluorescence immunophenotyping and interphase cytogenetics (FICTION). |
| Weber-Matthiesen K, Deerberg J, Poetsch M, Grote W, Schlegelberger B |
| Cytogenetics and cell genetics. 1995 ; 70 (3-4) : 243-245. |
| PMID 7789181 |
| |
| Clinical significance of Y chromosome loss in hematologic disease. |
| Wiktor A, Rybicki BA, Piao ZS, Shurafa M, Barthel B, Maeda K, Van Dyke DL |
| Genes, chromosomes & cancer. 2000 ; 27 (1) : 11-16. |
| PMID 10564581 |
| |
| Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. |
| Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A, Paietta E, Willman CL, Head DR, Rowe JM, Forman SJ, Appelbaum FR |
| Blood. 2000 ; 96 (13) : 4075-4083. |
| PMID 11110676 |
| |