Abnormal
Length of the Small Acrocentric Chromosomes
in Chronic Lymphocytic Leukemia
P. H. FITZGERALD
Cytogenetics
Unit,'
Christchurch
Hospital,
Christchurch,
New Zealand
SUMMARY
The
chromosomes
were examined
in 15 male
patients
and
3 female
patients
with
chronic lymphocytic leukemia and, for comparison, in 10 normal men and 5 normal
women.
All had grossly normal chromosomes, but analysis of the lengths of chromo
somes
Nos.
1, 2,
21,
22,
and
21, 22, and Y collectively,
men,
and
a similar
but
Y
showed
that
the
were significantly
nonsignificant
small
acrocentric
chromosomes,
Nos.
shorter in leukemic men than in normal
difference
in chromosomes
Nos.
21 and
22 was
present in leukemic and normal women.
No one chromosome was abnormally small,
and the shortness was probably due to a greater degree of spiralization and condensa
tion of all or some of the small acrocentric chromosomes.
This might be a secondary
effect of the leukemia,
or alternatively,
the greater
condensation
of the chromosomes,
with associated modification or suppression of the action of genes carried thereon,
could be a fundamental lesion closely concerned with the cause of chronic lymphocytic
leukemia.
It is suggested that such heteropykriotic
chromosomes may be the dense nuclear
condensations characterizing the Grumeléecell found in chronic lymphocytic leukemia.
The association of an inherited chromosome abnormal
ity, namely, absence of the short arm of 1 of the small
acrocentric chromosomes
(Ch'), with the occurrence of
chronic lymphocytic
leukemia in 2 siblings (9) and the
possibility that this chromosome abnormality might pre
dispose to the onset of the disease suggested that abnormal
ities of the No. 21 or No. 22 chromosome might also be
found in other cases of chronic lymphocytic
leukemia.
Careful
observation
this leukemia
centric
of the chromosomes
disclosed no abnormality
chromosomes
(4),
but
in several
nized by careful measurement
of the small acrocentric
chromosomes and comparison with a normal group.
The
present investigation
will be shown that
generally
sons.
shorter
in leukemic
I\IATERIALS
variation
Chromosome
was
lymphocytic
lymphocytic
males,
and
a similar size in both normal and leukemic persons.
therapy
possible
that
the small
defects,
readily
chromosomes
included
material,
such
may
be
1 Supported
small
readily
by
or loci concerned
and
and not
situation
with
deletion
in abnormal
visible,
the
Canterbury
of
&
them
might
Westland
material
be
for publication
March
2, 1965; revised
per
I)ivision
of
June
on
5
were made OH 15 cases of
leukemia
leukemia
normal
METHODS
in males,
in females,
females.
on 3 cases of
on 10 normal
Hematologic
been reported
for the patients
data,
examinations
with leukemia
(4). Chromosome measurements were made on patients
denoted in the earlier report as follows : Q32, Sh9, Te3, Te5,
1\I3, Nos. 2, 3, 4, 5, 6, 7, 9, 10, 12, 13, 21, 24, and 28. Pa
tients 24 and 28 originally presented as lymphosarcoma.
All of these patients showed grossly normal chromosomes
To measure the chromosomes,
the metaphase
plates
were projected by means of a Leitz microprojection
appa
ratus and a xenon lamp onto a mirror from a camera lucida
recog
the
Cancer Society of New Zealand.
Received
in normal
in cultures
of blood leukocytes,
which were also used for
chromosome
measurement.
The leukemic
Patients
were
selected because they showed a sufficient number of well
spread metaphase
plates suitable for measurement.
behavior.
of chromosome
some
locus,
of chromo
lymphocyte
deficiencies
lymph
of this
in a small or large deletion
resulted
Whereas
not
a locus
or control
than
data, and the results of chromosome
have already
if I of the pairs of small acrocentric
carried
production
whether
some
chromosomes
leukemia might have minor
less obvious thaI! the Ch' abnormality
apparent
on visual examination.
This
could come about
ocyte
acrocentric
It was
AND
measurements
chronic
chronic
in cases of chronic lymphocytic
persons
cases of
observed in their size and shape.
Such variation
may also
be seen in cells from normal persons, and the question arose
whether
the small acrocentric
chromosomes
aie indeed of
considered
It
defi
ciencies of this nature in any one of the small acrocentric
chromosomes but that these chromosomes as a whole were
in the small acro
considerable
was prompted
by this possibility.
there was no evidence for minute
28, 1965.
apparatus
and
were
thereby
projected
onto
the
1904
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bench
FITZGERALD—Abnormal
Length
beside the microscope.
The outlines of chromosomes Nos.
1, 2, 21, 22, and Y were drawn at a magnification of 3900.
When necessary, chromosomes nearer the periphery of the
field were centered before they were drawn.
A 10-.@scale
projected
through
the
same
which, when graduated
the
lengths
of the
optical
system
was
drawn,
in 0.1-p units, was used to measure
chromosomes.
Chromosome
lengths
were measured in 10 metaphase plates from each of the
leukemic persons and controls except 1\13, from whom only
S l)lates were measured.
Treatment of data.—The 2 main sources of variation
in
the measurement
of length of chromosomes
are the differ
cut states of chromosome
contraction
present in different
cells and the different lengths observed
between members
a chromosome
pair
within
a cell
different degrees of contraction
of the
small
relating
acrocentric
1905
Chromosomes
There might be a significant difference in the over-all
mean length of the small acrocentric chromosomes between
normal and heukemie groups.
(b) Variation in the mean
lengths
of the small acrocentric
chromosomes
leukemic
lersons
might be greater
than that
between
the
normal
presence
persons.
Such variation
of chromosome
congenital
(17).
The
effect
of
between cells on the length
chromosomes
can
be corrected
the length of these chromosomes
by
to the length of
chromosome
abnormalities,
possibly
somes
(g)
is significant
at
1 %
(mean
significant.
contract
and
lengthen
to a
greater extent than do the small acrecentric chromosomes,
even after differences in size are considered (3). Thus, a
simple
relationship
between
will not give an accurate
different
degrees
chromosomes.
these
groups
correction
of contraction
An accurate
of chromosomes
of the variation
of the
small
correction
due to
acrocentric
can be achieved,
of acquired
origin
and not necessarily present in all cells, in leukemic persons.
Analysis
of male data.—The results of analyses of
variance on the data from normal and leukemic males are
shown iii Table 1.
a) The variation between normal and leukemic g1'ou@)s
in over-all mean length of the 5 Nos. 21, 22, and Y chromo
mean length of these chromosomes
because it has been shown that the
2 chromosomes
of
leukemic
persons.
(c) Variation
in the mean lengths of
the small acrocentric
chromosomes
between
cells within
making this correction
1 and
PossiblY
all cells, in some or all
another
independent
group of chromosomes—in
this case
the Nos. 1 and 2 chromosomes.
Care must be taken in
Nos.
would suggest
abnormalities,
origin and affecting
between
occurring
leukemic persons might be greater than that between cells
within normal persons.
Such variation
would suggest
RESULTS
of
of Acrocentric
degree
of
states
cause
freedom)
This
; this
difference
of chromosome
no significant
square
indicates
is
that
62.06
for
1
1-j.i-shorter
in the leukemic group is
not
an
coiitraction
difference
=
the
effect
of
different
in different
is found
between
cells
normal
be
and
leukemic groups in the lengths of the a group chromosomes
(mean square = 84.82 for 1 degree of freedom).
b) The variation between people in mean length of the g
chromosomes is significant at 1 % in both normal (mean
of long
square = 7.82) and leukemic
(mean square 3.70) groups.
This highly significant variation
is probably
due largely to
and short chromosomes, by taking from the small acro
centric chromosomes that component of their variation
different degrees of chromosome contraction because it is
also present in the mean length of the a chromosonies
without
interference
which
by the differential
can be correlated
chromosomes
cOrrectiOli
contraction
with variation
of the Nos. 1 and 2
as shown by a test of covariance.
iS made
Thus the
(mean
square
124.35)
correlated
by the function
for
normal
2
(@)
(correlation
ill Tables
1 and
2.
The 2 chromosomes
difference
in length
of a pair may show considerable
in the same
this effect between
the individual
somes,
length
the
different
a2
summed
of
the
cell (17).
4 chromosomes
cell is used as a basis for the correction
chromosome
distinguish
contraction.
accurately
To minimize
Nos. 1 and 2 chromo
It is not always
the Nos.
in
of variation
21 and
each
due to
I)Ossible to
22 pairs
of acro
centric chromosomes.
The Y chromosome can usually
be distinguished, but not always, because this chromosome
shows
considerable
polymorphism
(10,
17).
To
avoid
error due to incorrect identification of the small chromo
somes, the lengths of all 5 small acrocentric chromosomes
in each
cell were
group.
The analysis
added
together
and
treated
of the measurement
as a single
data therefore
degrees
173.96
and
for
leukemic
in the a and g groups
coefficient
0.834 and in leukemic
g
=
and this variation
group
in
normal
= 0.670).
of chromosome
=
is strongly
group
=
The effect of
contraction
on
the
g
chromosomes is corrected by taking out the correlated
variation of the g and a groups, when the Nos. 21, 22, and
Y chromosomes
still show highly significant variation
between people in both the normal (mean square = 2.638)
and the leukemic
(mean square
= 2.076) groups.
The
variation
is similar in both groups, and there is no indica
tion of any variation peculiar to the leukemic grout).
c) The variation between cells within people in length of
the g chromosomes
is also significant
normal
(mean square
square
=
1.17)
chromosomes
in both
0.692
groups.
Again
the
with the a chromosomes
groups
and
at 1 % in both
= 1.06) and the leukemic
(correlation
in leukemic
coefficient
group
covariance
the
(mean
of the g
is highly significant
in normal
= 0.763.
When
group
this
=
cor
related variation is taken out, the remaining variation be
tween cells of the g chromosomes has a mean square value
consisted
essentially
of a comparison
between normal and
and leukemic persons of the summed lengths of the 4 Nos.
21 and 22 chromosomes
and, in males, of the Y chromo
some (g) after correction for contraction
difference based on
the summed lengths of the 4 Nos. 1 and 2 chromosomes
(a).
of 0.562
Analyses of variance were carried out on the full data to
provide information on the following 3 possibilities.
(a)
of any
group.
in the
Although
normal
group
and
the significance
0.494
in the
leukemic
of these values is not
tested, their closeness indicates that the variation
between
cells of the Nos. 21, 22, and Y chromosomes
is similar in
both normal
and leukemic
variation
Analysis
peculiar
of female
people ; there is no indication
to the
leukemic
daia.—The results
cells.
of analyses
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1965 American Association for Cancer Research.
of
Cancer Research
1906
TABLE
MALE
@
21, 22, and Y chromosomes
@
@2
@
@
GRoUP ANALYZED
OF
\ARIANCE
are represented
by g.
The
d f
Sum of
cross
products
Sum of
squares
Mean
square
1
25
84.82
3306.58
143.76
478.32
9
1565.63
2769.32
173.96b
276.95
90
for normal males and 30.65 .@for
mean
for g is 10.20
@tfor
normal
ag
d.f.
Normal and leukemic
Between groups
Between people within groups
Normal
Between people
Between cells withiii people
1965
1
ANALYSES
Summed lengths of Nos. 1 and 2 chromosomes are represented by a. The mean for a is 31.84
leukemic
males. Summed lengths of Nos.
males and 9.19 ,@for leukemic
males.
@
i)@@TA
Vol. 25, December
72.55
84.82―
30.77
(ag)2!
.‘
Correla
Mean
@2
Regression
tion
square
(g/a)
(a, g)
square
62.06
122.25
62 .06―
70.42
95.93
7.82―
106―
356.60
2
. .
Mean
Sum of
squares
5.32
9
89
23.74
2.638b
0.834―
50.02
0.562
0 . 692
29.07
66.15
0 .494
0.177―
0.129―
Between chromosomes within
cells
400
Leukemi
125.58
Between people
14
Between cells within people
135
Between chromosomes
cells
600
U Not
1740.95
4993.74
124.3&'
36.99
158.33
3 . 70― 14
l.17b
134
170.40
0.28
201.37
51.83
678.46
2.076― 0 . 670― 0.116―
0.763― 0136―
within
significant.
I; Probability
less
than
1@.
TABLE
FEM:@LE
@
0.31
C
Summed
lengths
of Nos.
for the leukemic
mal females
1 and 2 chromosomes
2
I)@@TA: AN.@LYsEs
are represented
by a.
OF VARIANCE
The mean
female. Summed lengths of Nos. 21 and 22 chromosomes
and 7.03 @zfor leukemic
for a is 31.03
are represented
@z
for the
by g.
normal
female
and
28.03
The mean for g is 7.66 z for nor
females.
@
g2
—@
@‘
d.f.
GROUP ANALYZED
@
Sum of
squares
Mean
square
Sum of
cross
products
Sum of
squares
d.f.
g2 —
Mean
square
(@jg)2@
Mean
Correla
tion
square
Regression
(g/a)
(a, g)
Normal and leukemic
Between groups
Between
people
within
groups
Normal
Between people
Between cells within people
Between
chromosomes
withi
150 . 20―
45.45
31.42
81.94
6.57
32.57
4
83.42
1544.35
20.86―
31 .63
143.65
19.13
4.78―
34.32
30.35
0 .67's
24.66
0.16
6.57―
5.43
4
44
13.61
16.99
3 .403― 0 .792a
0 .386
0 .663
0.379―
0 .093―
ii
150
Between people
Between cells within people
Between chromosomes withiui
cells
@
150.20
272.68
45
cells
Leukemic
@
1
6
2
189.26
22
752.80
94.63― 50.31
34.22
72.78
75
13.44
6. 72b
15.87
0 . 72b
13.90
0.185
2
21
4.39
2.197c
0. 997c
0 .266―
8.84
0.421
0 .666'
0.097―
a Not significant.
@
b Probability
less
than
1%.
C Probability
less
than
5@
variance
on the data
are shown in Table
and
greater
thasi
from normal and leukemic
2. The 0.63-j.@ difference
females
between
normal and leukemic groups in the over-all length of the g
(Nos. 21 and 22) chromosomes is not significant (mean
square
= 6.57),
nor
is there
any
significant
over-all mean length of the a chromosomes
150.20).
As in the male data, a highly
variation
tion between people in length of the g chromosomes
in
both
normal
and
leukemic
groups
even
in the
(mean square =
significant
varia
after
occurs
correction
for different
degrees of chromosome
contraction
(mean
square for normal = 3.403 and for leukemic
= 2.197).
A
similar variation is found in the length of the g chromo
somes between cells within people.
The variations both
between
persons
and between
cells are similar
in normal
and leukemic
groups, and again there is no indication
any variation
peculiar
Variation
to the leukemic
of
group.
of large and small chromosomes.—Following
the demonstration
that
the Nos.
1 and 2 chromosomes
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1965 American Association for Cancer Research.
on
FITZGERALD—AbnOrmal
Length
of Acrocentric
1907
Chromosomes
tric chromosomes showed a significant variation between
cells and also between people in both males and females.
This variation between cells and between people was of the
12
same
of the
K.
K
,
g
studies
,
.
/
K
leukemic
gave
and
no evidence
normal
groups
of the
presence
; this
/
9
@0'
in the
to pick
up minute
differences
in the
length
25
3,5
3'O
somes
4'O
length
of 1 chromosome
CHART 1.—The regressions
in the 15 males
was about
a
NORMAL
— K
LEUKEMIC
——— S
of g (summed
lengths
of the Nos.
21, 22, and Y chromosomes) on a (summed lengths of the Nos. 1
would
be diluted
in the
these
chromosomes
significant.
with
1 @z
shorter
The
22 chromosomes
0.63 @Lshorter
chronic
in 10 normal
over-all
lymphocytic
than the over-all
mean
leukemia
mean length
males ; this difference
length
in the 3 females
than the over-all
of the
with
mean
Nos.
of
was
21 aimd
this disease was
length of these
chromosomes in the 5 normal females.
This difference
was not significant, possibly because there were too few
data from all cells. The points shown are the means for each female cases of leukemia in this sample to give a critical
person only.
For the normal, öb(standard deviation
of the re
result.
Because of the wide variation between people, it
gression coefficient) is ±0.0132,and for the leukemic, ö@
is ±0.0098. was not possible to tell whether this shortness of the small
acrocentric chromosomes was present in all cases of leu
kemia
or whether some cases did not show it. However,
the one hand and the small acrocentric chromosomes on
the distribution pattern of means for each person in Chart
the other hand do not contract to the same degree propor
1 would indicate that it was present in most male cases.
tional to their size (3), an investigation was made to see
The summed lengths of the small acrocentric chromo
if this contraction behavior was of the same order in both
somes
in males
ranged
from
8 to 13 @tapproximately
and
normal and leukemic groups.
The relative variation in
averaged
about
10.5
or
an
average
length
of
just
above
length of the long and short chromosomes with different
2 for each of the 5 small acrocentric
chromosomes.
If the
degrees of contraction was established by calculating the
1-j.@difference between leukemic and normal chromosomes
regression
of the short
chromosome
lengths
(g) on the long
in 1 of the
chromosomes,
about
chromosome lengths (a) from the data from all cells for was due to a deficiency
half of the chromosome would be missing, and such an
normal and leukemic groups, both male (Chart 1) and
abnormality
would be readily visible.
The variation in
female (Chart 2). These regressions were calculated from
size of the small acrocentric chromosomes was usually not
the g and a measurements
of the normal and leukemic
of this order, and no such consistent difference was found,
cells, but because the points were too numerous in the male
data, Chart 1 shows the means for each person only. The nor was there any evidence of it in the measurement
data.
Rather, the decrease in length in leukemic persons
regressions for both normal and leukemic data are signifi
would appear to be due to a change in the entire group of
cant
at 1 % in both
males
and
females
(Tables
1, 2) and
small acrocentric chromosomes or in some of them. Demon
follow lines of similar slope, which do not differ significantly
stration of the presence of the length difference in females
from one another; the heterogeneity regression has a mean
as well as in males would indicate that the acrocentric
square of 0.612 for 3 d.f., which is not significant (Table 3).
autosomes were mainly involved, but this was not estab
There is therefore no evidence of any difference between
lished
by the present data, and an effect of the Y chromo
normal and leukemic persons in the relative contraction of
some must also be considered.
Minute deletion of each
the long and short chromosomes.
acrocentric chromosome is unlikely, and the shortening is
DISCUSSION
probably due to a greater degree of condensation of these
Consideration
of the significance of this
The analysis of the measurement data demonstrated chromosomes.
chromosome
contraction
is
complicated
by uncertainty
that, after allowance had been made for different degrees of
whether the cells examined in the leukemic patients were
chromosome contraction, the length of the small acrocen
and 2 chromosomes) for normal males (solid line) and leukemic
males
@
of 1
summed lengths of all.
The measurement
data did show, however, that the
over-all mean length of the Nos. 21, 22, and Y chromo
8
@
part
of an ab
small acrocentric chromosome is limited.
Indeed, it has
been suggested that an abnormality
in any one chromo
some large enough to be detected by length measurements
would be readily visible (11, 17). The present experience
would agree with this, especially as it involved a group of
chromosomes
of small size, which were impossible to
separate accurately, with the result that a small difference
/
‘p.
S
in both
analysis
normal small acrocentric chromosome, whether congenital
or acquired somatically,
associated with leukemia.
It
should be realized, however, that apart from the large
amount of apparently
natural variation,
which could
obscure such abnormalities,
the ability of measurement
11
ic
order
(broken
line).
The
regressions
were
calculated
from
the
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1965 American Association for Cancer Research.
Vol. 25, December
Cancer Research
1908
1965
K
K
9
K
K
K
K
K
KK
S
5K
K
8
S
K
K
S
7
.
75
K K
K
5*
g
7
7
7.
7
K
K
S
.7
K
S
6-
K
K
K
55
K
20
S
K
25
35
30
45
40
a
NORMAL
LEUKEMIC
K
———•
CHART 2.—Plot of g (summed lengths of the Nos. 21 and 22 chromosomes)
against a
(summed lengths of the Nos. 1 and 2 chromosomes)
for all cells from normal and leukemic
females, and regressions of g on a for normal females (solid line) and leukemic females
(broken line) . For the normal regression Sb ‘S
±0.0198,and for the leukemic regression 5b
is ±0.0247.
TABLE 3
ANALYSIS OF VARIANCE OF g BETWEEN CELLS WITHIN CLASSES
AND REGRESSION ON a
Summed lengths of Nos. 21, 22, and Y chromosomes are rep
resented by g; summed lengths
are represented by a.
of Nos. 1 and 2 chromosomes
buildup of lymphocytes in this leukemia
lead to metabolic deficiencies, as a result
might tend toward a state of pyknosis,
the 1st stages by a general condensation
of the chromosomes.
As the rates of
elongation differ between small and large
it is possible
squareTotal
Regressiond.f.@i'@r@Mean
regression
Mean regression
(0.1328 ±0.0070)
Heterogeneity regression
Error
Between cells within classes (total)4
a Probability
b Not
less
than
1
3
317
240 .66
1.83
212.87
0.612―
0.672
321242.49
455.36240.658°
acrocentric
stages
of pyknosis
the small
chromosomes
as a whole,
acrocentric
chromosomes
in leukemic
persons
is
probably due to a precocious condensation
and spiraling
of the chromonemata;
i.e., the small acrocentric chromo
somes or some of them are out of phase with the normal
normal or leukemic lymphocytes,
a problem that is fully
discussed
in an earlier paper (4).
If the cells were non
the abnormal
condition that
in the early
or the
begin to condense earlier than the larger chromosomes.
The presence of abnormal mitoses in HeLa cells suggests
that cells in such early stages of pyknosis are capable of
mitosis (2).
Conversely, shortening of the chromosomes could reflect
a basic lesion, causing leukemia.
The smaller size of the
small
1%.
significant.
leukemic,
inherited
that
chromosomes,
would inevitably
of which the cells
characterized
in
and spiralization
condensation
and
chromosomes (3),
shortness
could
confers a greater
represent
likelihood
an
of
condensation
and
spiralization
pattern
of
the
cell
(allo
cycly) and show a degree of heteropyknosis.
Hetero
pyknosis in a more extreme form is well known in 1 of the
x
chromosomes
in female
cells,
and
it is believed
that
this
nantly leukemic (4), the abnormal shortness of the small
acrocentric
chromosomes
could have several different
explanations,
such as an abnormal response of leukemic
cells to in vitro culture or to preparative procedures.
Or
chromosome forms the sex chromatin body observed in the
resting stage of such cells. There is now strong evidence
from autoradiographic
studies that the heteropyknotic
X
chromosome shows delayed synthesis of deoxyribonucleic
acid (DNA) (1, 5—7,13—15,18) possibly as a result of its
more tightly coiled state (7). This suggests that the small
the greater condensation of the small acrocentric chro
acrocentric
mosomes might be a secondary effect of a physiologic
state developing in the leukemic cell. The abnormal
abnormal timing in the synthesis of DNA in chronic
lymphocytic leukemia.
The presence of definite patterns
development
seems more
of chronic
lymphocytic
leukemia.
If, as
probable,
the cells examined
were predomi
chromosomes,
or some
of them,
might
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1965 American Association for Cancer Research.
show
FITZGERALD—Abnormal
Length
of Acrocentric
of DNA synthesis in human chromosomes is now well
established, and Taylor (19) has suggested that various
chromosomes or parts of chromosomes have a genetically
controlled sequence in duplication, which may have some
functional
significance.
Grumbach
et at. (8) have ex
tended this view, suggesting that the allocylic behavior of
the X chromosome,
its delayed duplication,
and the
associated
modification
or suppression
of its genetic
activity may be only the most conspicuous example of a
more general phenomenon
implicating all chromosomes.
According to this concept, the precocious coiling of chro
mosomes
and
the
associated
delayed
DNA
synthesis
constitute a mechanism that modifies the action of genes
carried on the autosomes and may play an important
part in the expression of genes in cellular differentiation
and in the regulation of morphogenesis.
It is tempting to
suggest that the fundamental
cytic leukemia
is an acquired
lesion in chronic lympho
allocycly
of some of the
small acrocentric autosomes (possibly the No. 21 pair)
whereby they show precocious coiling, possibly delayed
synthesis
of DNA,
and
associated
modification
or sup
pression of a genetic locus, or loci, concerned with lympho
cyte production or with a control mechanism maintaining
the normal levels of these cells. Caution in accepting this
suggestion is indicated by the similar finding of abnormally
short small acrocentric autosomes in Marfan's syndrome
(12). Further information must be sought on the nature
of this variation in chromosome length, the possible in
volvement of other chromosomes, and the extent of its
occurrence in other conditions.
At the same time, the
fairly uniform occurrence of this chromosome shortening
in chronic lymphocytic leukemia, providing that it can be
confirmed in further series of cases, would indicate that it
is not incidental to, but closely associated with, this disease
whether as cause or effect. In this respect it would be
interesting to consider the possible role of virus infection in
initiating such chromosome allocycly.
The formation of the sex chromatin body by the hetero
pyknotic X chromosome in female cells suggests that the
greater condensation of the small acrocentric chromosomes
in chronic lymphocytic leukemia might also be visible as
heteropyknotic
bodies in resting nuclei.
Such is possibly
the explanation
of the Grumelée cell reported to char
acterize
chronic
lymphocytic
nuclei of these lymphocytes
leukemia
(16).
The
show a checkerboard
resting
pattern
of dense nuclear condensations, which could well be the
small acrocentric chromosomes, and perhaps other chro
mosomes, in a heteropyknotic
condition or in the early
stages
of pyknosis.
1909
Chromosomes
ACKNOWLEI)GMENTS
I am indebted to Dr. B. I. Hayman and Dr. K. Hastings for
advice on statistical treatment of the chromosome measurement
data; to Miss Elizabeth Stevenson for computation;
to Miss An
gela Adams for assistance in selection of cells suitable for meas
urement;
and to Dr. F. W. Gunz for drawing my attention
to the
Grumelée cell.
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Abnormal Length of the Small Acrocentric Chromosomes in
Chronic Lymphocytic Leukemia
P. H. Fitzgerald
Cancer Res 1965;25:1904-1909.
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