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-Y, Y loss in leukemia
Daniel L Van Dyke
Department of Medical Genetics, Henry Ford Health System, 2799 West Grand Boulevard, Clara Ford
Pavillion, Detroit, MI 48202, USA (DLV)
Published in Atlas Database: January 2001
Online updated version : http://AtlasGeneticsOncology.org/Anomalies/YlossID1089.html
DOI: 10.4267/2042/37712
This article is an update of: Desangles F. Y loss in leukemia. Atlas Genet Cytogenet Oncol Haematol.1999;3(2):80-81.
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2001 Atlas of Genetics and Cytogenetics in Oncology and Haematology
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.
Identity
Note
Loss of the Y chromosome from individual metaphases
is common in metaphase cells from both PHAstimulated lymphocytes and spontaneously dividing
bone marrow cells. The frequency of Y loss is greater
in older men, and the size of the 45,X,-Y cell
population probably increases gradually with
advancing age. (In females, a corollary loss of one X
chromosome also occurs with advancing age.) This
natural phenomenon challenges our ability to
distinguish between a normal and a disease-associated
45,X,-Y clone.
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.
Clinics and pathology
Disease
Cytogenetics
-Y is frenquently observed in myeloproliferative
diseases (MPD), myelodysplasic syndromes (MDS),
acute non lymphocytic leukemias (ANLL), and can
also be seen in lymphoproliferations.
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
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 preremission metaphases. These observations support the
interpretation that the leukemia cell karyotype is 45,X,Y.
Atlas Genet Cytogenet Oncol Haematol. 2001; 5(1)
56
-Y, Y loss in leukemia
Van Dyke DL
XXXV. The missing Y in acute non-lymphocytic leukemia
(ANLL). Cancer. 1980 Jan 1;45(1):84-90
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).
Holmes RI, Keating MJ, Cork A, Trujillo JM, McCredie KB,
Freireich EJ. Loss of the Y chromosome in acute myelogenous
leukemia: a report of 13 patients. Cancer Genet Cytogenet.
1985 Jul;17(3):269-78
. Acute myelogenous leukemia with an 8;21 translocation. A
report on 148 cases from the Groupe Français de
Cytogénétique Hématologique. Cancer Genet Cytogenet. 1990
Feb;44(2):169-79
Nowinski GP, Van Dyke DL, Tilley BC, Jacobsen G, Babu VR,
Worsham MJ, Wilson GN, Weiss L. The frequency of
aneuploidy in cultured lymphocytes is correlated with age and
gender but not with reproductive history. Am J Hum Genet.
1990 Jun;46(6):1101-11
Probes
All available probe for the Y chromosome.
Additional anomalies
. Loss of the Y chromosome from normal and neoplastic bone
marrows. United Kingdom Cancer Cytogenetics Group
(UKCCG) Genes Chromosomes Cancer. 1992 Jul;5(1):83-8
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.
Abeliovich D, Yehuda O, Ben-Neriah S, Or R. Loss of Y
chromosome. An age-related event or a cytogenetic marker of
a malignant clone? Cancer Genet Cytogenet. 1994
Aug;76(1):70-1
Kirk JA, VanDevanter DR, Biberman J, Bryant EM. Y
chromosome loss in chronic myeloid leukemia detected in both
normal and malignant cells by interphase fluorescence in situ
hybridization.
Genes
Chromosomes
Cancer.
1994
Nov;11(3):141-5
Genes involved and proteins
Note
Genes involved, if any, are unknown.
Riske CB, Morgan R, Ondreyco S, Sandberg AA. X and Y
chromosome loss as sole abnormality in acute nonlymphocytic leukemia (ANLL) Cancer Genet Cytogenet. 1994
Jan;72(1):44-7
To be noted
Note
It is not known whether the Y chromosome loss is the
critical mutational event. Likewise, it is not known
whether the Y chromosome loss is a secondary genetic
change, or if the critical (submicroscopic) genetic
change simply occurs by chance in a -Y cell.
Speculatively, loss of the Y could provide a
proliferative advantage simply because it tends to
replicate late in S-phase. Its loss might therefore
shorten the cell cycle slightly.
Weber-Matthiesen K, Deerberg J, Poetsch M, Grote W,
Schlegelberger B. Clarification of dubious karyotypes in
Hodgkin's
disease
by
simultaneous
fluorescence
immunophenotyping and interphase cytogenetics (FICTION).
Cytogenet Cell Genet. 1995;70(3-4):243-5
Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil
KS, Mohamed A, Paietta E, Willman CL, Head DR, Rowe JM,
Forman SJ, Appelbaum FR. Karyotypic analysis predicts
outcome of preremission and postremission therapy in adult
acute myeloid leukemia: a Southwest Oncology Group/Eastern
Cooperative Oncology Group Study. Blood. 2000 Dec
15;96(13):4075-83
References
Wiktor A, Rybicki BA, Piao ZS, Shurafa M, Barthel B, Maeda K,
Van Dyke DL. Clinical significance of Y chromosome loss in
hematologic disease. Genes Chromosomes Cancer. 2000
Jan;27(1):11-6
Pierre RV, Hoagland HC. Age-associated aneuploidy: loss of Y
chromosome from human bone marrow cells with aging.
Cancer. 1972 Oct;30(4):889-94
Berger R, Bernheim A. Y chromosome loss in leukemias.
Cancer Genet Cytogenet. 1979;1:1-8.
This article should be referenced as such:
Van Dyke DL. -Y, Y loss in leukemia. Atlas Genet Cytogenet
Oncol Haematol. 2001; 5(1):56-57.
Abe S, Golomb HM, Rowley JD, Mitelman F, Sandberg AA.
Chromosomes and causation of human cancer and leukemia.
Atlas Genet Cytogenet Oncol Haematol. 2001; 5(1)
57