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International Journal of Molecular Medical Science
6
1.2 Correlation between expression levels of
Ku
and Ikaros-regulated lymphoid priming genes
IK has been shown to direct lymphoid priming during
the earliest stages of lymphocyte ontogeny by
upregulating the expression of specific genes (Yoshida
et al., 2010). Notably, 13 transcripts representing 12
IK-regulated lymphoid priming genes were
significantly upregulated in human lymphocyte
precursor cells from primary bone marrow specimens
of pediatric patients with ALL expressing high levels
of both
IKFZ1
and
Ku
(Figure 2). The 5 most
significantly upregulated lymphoid priming genes in
specimens with high
Ku
expression were
SOX4
(0.64
SD units, P = 1.4 × 10
-14
),
CSF1R
(0.52 SD Units, P =
8.6 × 10
-11
),
IL7R
(0.52 SD units, P = 5.1 × 10
-11
),
DNTT
(0.51, P = 1.6 × 10
-10
),
NOTCH1
(0.47, P = 1.4
× 10
-14
) (Figure 2). Hierarchical cluster analysis
revealed a subset of 3 genes (
RAG1
,
DNTT
and
MEF2C
(2 transcripts)) that were highly co-regulated
with 3 transcripts of
IKZF1
(Figure 2). This striking
correlation between the expression levels of IK-regulated
lymphoid priming genes and
Ku
expression levels
indicates that
Ku
is involved in the regulation of IK
function in primary human lymphocyte precursors.
Table 1
Ikaros
target gene expression levels in human lymphocyte precursors according to
ikzf1
and
ku
transcript levels
Affy ID
Genesymbol
Ku
transcript levels
Ikaros
transcript levels
StdDev Units
StdDev Unites
[High
Ku
(N=314)
T-test
[High
Ikaros
(N=302)
T-test
-Low
Ku
(N=324)]
P-value
-Low
Ikaros
(N=318)]
P-value
205273_s_at
PITRM1
1.21
1.2 × 10
-59
0.52
3.8 × 10
-10
213761_at
MDM1
1.13
2.2 × 10
-49
0.84
1.7 × 10
-26
205884_at
ITGA4
1.19
2.7 × 10
-49
0.97
4.2 × 10
-32
204709_s_at
KIF23
1.13
1.3 × 10
-46
0.36
7.4 × 10
-6
204117_at
PREP
1.06
1.5 × 10
-43
0.72
3.0 × 10
-17
37950_at
PREP
1.04
1.0 × 10
-39
0.67
2.8 × 10
-16
213416_at
ITGA4
1.05
1.9 × 10
-39
0.84
1.8 × 10
-26
220397_at
MDM1
0.98
1.5 × 10
-36
0.82
8.7 × 10
-25
205885_s_at
ITGA4
0.99
3.0 × 10
-35
0.86
6.9 × 10
-26
205352_at
SERPINI1
0.64
2.4 × 10
-16
0.71
2.9 × 10
-18
203474_at
IQGAP2
0.62
3.6 × 10
-14
0.75
8.5 × 10
-21
219748_at
TREML2
0.50
5.8 × 10
-10
0.47
9.6 × 10
-9
200771_at
LAMC1
0.48
2.2 × 10
-9
0.82
3.0 × 10
-25
221250_s_at
MXD3
0.49
2.4 × 10
-9
0.23
5.7 × 10
-3
201034_at
ADD3
0.47
5.9 × 10
-9
0.65
1.3 × 10
-14
201752_s_at
ADD3
0.41
9.2 × 10
-8
0.58
4.9 × 10
-12
213745_at
ATRNL1
0.44
1.1 × 10
-7
0.31
3.0 × 10
-4
217599_s_at
MDFIC
0.42
3.0 × 10
-7
0.55
1.1 × 10
-11
205882_x_at
ADD3
0.38
1.0 × 10
-6
0.57
1.2 × 10
-11
211675_s_at
MDFIC
0.35
1.2 × 10
-5
0.49
3.1 × 10
-10
207821_s_at
PTK2
0.32
1.2 × 10
-4
0.44
5.3 × 10
-8
203305_at
F13A1
0.30
1.9 × 10
-4
0.46
7.8 × 10
-9
201753_s_at
ADD3
0.26
5.5 × 10
-4
0.56
1.4 × 10
-11
218706_s_at
GRAMD3
0.27
7.4 × 10
-4
0.30
2.6 × 10
-4
200872_at
S100A10
0.25
1.5 × 10
-3
0.16
4.8 × 10
-2
210815_s_at
CALCRL
0.24
2.9 × 10
-3
0.29
5.6 × 10
-4
204672_s_at
ANKRD6
0.23
5.6 × 10
-3
0.35
2.4 × 10
-5
208642_s_at
XRCC5
2.16
1.8 × 10
-189
0.97
1.3 × 10
-32
208643_s_at
XRCC5
2.13
1.1 × 10
-187
1.11
1.1 × 10
-44
200792_at
XRCC5
2.05
1.2 × 10
-160
0.75
4.8 × 10
-20
205038_at
IKZF1
0.95
3.4 × 10
-36
2.20
3.3 × 10
-186
205039_s_at
IKZF1
0.50
1.2 × 10
-11
2.00
9.8 × 10
-141
216901_s_at
IKZF1
0.69
2.0 × 10
-18
1.70
3.8 × 10
-95
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