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Supplementary Information

Treatment Specific Changes in Gene Expression Discriminate in vivo Drug Response
in Human Leukemia Cells

C. Selection of Discriminating Genes

Figure 3: Discriminating genes by different gene selection methods.

Figure 3: Discriminating genes by different gene selection methods.

The overlap among the 500 top-ranked probe sets identified by linear discriminant analysis (LDA), the 500 top-ranked probe sets identified by ANOVA and the 4x100 top-ranked probe sets (359 and 352 unique probe sets) identified by distinction calculation (one-versus-all) are shown as percentage overlap. The circle indicates the overlap among all three methods. (a) Probe sets for post-treatment expression and (b) probe sets for fold-change in expression.

Table 2: Discriminating genes by fold-change and post-treatment expression.

Shown in the following table are the 27 probe sets (26 genes, 18%) that were present in both sets of genes discriminating among the four treatments (the 150 probe sets based on fold-change and the 150 probe sets based on post-treatment expression), as determined by LDA

probe set ID accession number gene name
34967_at AF001549 RNA polymerase I transcription factor RRN3
34577_at U10694 melanoma antigen, family A, 9
41415_at L36720 bystin-like
37781_at AB023138 neurexin 2
1916_s_at V01512 c-fos
39286_at D64109 transducer of ERBB2, 2
37662_at AI701164 ubiquitin-conjugating enzyme E2G 1
38082_at AB014550 KIAA0650 protein
31872_at X79201 synovial sarcoma translocation, chromosome 18
37244_at AA746355 ubiquitin carboxyl-terminal esterase L3
2065_s_at L22473 BCL2-associated X protein
38386_r_at U34683 glutathione synthetase
2000_at U26455 ataxia telangiectasia mutated
38615_at AF097021 differentially expressed in hematopoietic lineages
37105_at M16117 cathepsin G
36710_at Z38026 cathelicidin antimicrobial peptide
37096_at M34379 elastase 2, neutrophil
33963_at M96326 azurocidin 1 (cationic antimicrobial protein 37)
38879_at D83664 S100 calcium binding protein A12 (calgranulin C)
41471_at W72424 S100 calcium binding protein A9 (calgranulin B)
41096_at AI126134 S100 calcium binding protein A8 (calgranulin A)
32821_at AI762213 lipocalin 2 (oncogene 24p3)
31506_s_at L12691 defensin, alpha 3, neutrophil-specific
31793_at AL036554 defensin, alpha 3, neutrophil-specific
37864_s_at Y14737 immunoglobulin heavy constant gamma 3
37391_at X12451 cathepsin L
2081_s_at L07032 protein kinase C, theta

Fig. 4: Hierarchical clustering of changes in expression for selected genes.

Hierarchical clustering of fold-change in gene expression after treatment, using the 150 most discriminating probe sets (124 genes and 23 ESTs; P=0.017) selected by LDA. Each column represents a patient (n=60) labeled according to the treatment given (color legend at the bottom) and each row represents a gene probe set. Hierarchical clustering (top dendrogram) correctly grouped each patient into the four treatments, with one exception. Red indicates up-regulation and green indicates down-regulation in gene expression (fold-change) after treatment, according to the fold-change scale in the upper right. Solid lines enclose groups of genes showing greatest difference for the treatment indicated. These are the same data as shown in Fig. 4 of the primary manuscript, but with gene names provided. Hierarchical clustering performed after removing either one of two replicate probe sets for three genes did not cause a difference in clustering (data not shown).

Fig. 4: Hierarchical clustering of changes in expression for selected genes.

Table 3: Discriminating genes by one-versus-all distinction calculation.

To distinguish one treatment from all other treatments, we also computed distinction values for each probe set. The 353 gene probe sets are rank-ordered according to the distinction value (DC) for each treatment [HDMTX (HD), HDMTX+MP (HDMP), LDMTX+MP (LDMP), MP], (-) indicates genes down-regulated and (+) genes up-regulated. Additionally, we performed one thousand permutations with random class labels to obtain the P values for each probe set. The P value was defined as the probability of obtaining by random assignment distinction values less than or equal to the observed. Among a large number of probe sets with P values <0.01, 50 probe sets with the largest distinction values were selected, listed here are the top 50 probe sets for each treatment.

probe set ID accession number gene name >HD DC HDMP DC LDMP DC MP DC HD P val. HDMP P val. LDMP P val. MP P val. rank
41471_at W72424 S100 calcium binding protein A9 (calgranulin B) 0.9 -0.3 -0.5 -0.4 0.000 0.139 0.001 0.017 HD+01
35926_s_at AF004230 leukocyte immunoglobulin-like receptor, subfamily B 0.8 -0.4 -0.4 -0.3 0.000 0.017 0.011 0.088 HD+02
31793_at AL036554 defensin, alpha 3, neutrophil-specific 0.8 -0.3 -0.4 -0.3 0.000 0.060 0.008 0.122 HD+03
41096_at AI126134 S100 calcium binding protein A8 (calgranulin A) 0.7 -0.4 -0.4 -0.3 0.000 0.057 0.010 0.077 HD+04
34703_f_at AA151971 clone=IMAGE-588365 0.6 -0.1 -0.4 -0.4 0.000 0.660 0.014 0.029 HD+05
41126_at AA978353 phosphoserine aminotransferase 0.6 -0.2 -0.3 -0.3 0.000 0.218 0.057 0.133 HD+06
37105_at M16117 cathepsin G 0.6 -0.2 -0.4 -0.2 0.000 0.206 0.006 0.229 HD+07
38087_s_at W72186 S100 calcium binding protein A4 0.6 -0.5 0.0 -0.3 0.000 0.008 0.712 0.059 HD+08
39119_s_at AA631972 natural killer cell transcript 4 0.6 -0.1 -0.4 -0.2 0.000 0.737 0.012 0.133 HD+09
32793_at X00437 T cell receptor beta locus 0.6 0.0 -0.4 -0.4 0.000 0.964 0.012 0.035 HD+10
33963_at M96326 azurocidin 1 (cationic antimicrobial protein 37) 0.6 -0.3 -0.4 -0.2 0.001 0.095 0.008 0.430 HD+11
34702_f_at M27826 endogenous retroviral protease 0.6 -0.1 -0.4 -0.2 0.000 0.404 0.010 0.266 HD+12
38363_at W60864 TYRO protein tyrosine kinase binding protein 0.5 -0.2 -0.2 -0.3 0.000 0.172 0.140 0.108 HD+13
2000_at U26455 ataxia telangiectasia mutated 0.5 -0.3 -0.4 0.0 0.000 0.071 0.038 0.570 HD+14
38615_at AF097021 differentially expressed in hematopoietic lineages 0.5 -0.2 -0.4 0.0 0.000 0.281 0.010 0.712 HD+15
32749_s_at AL050396 filamin A, alpha (actin binding protein 280) 0.5 -0.3 -0.2 -0.2 0.000 0.125 0.260 0.225 HD+16
2065_s_at L22473 BCL2-associated X protein 0.5 -0.5 -0.1 -0.1 0.000 0.007 0.688 0.436 HD+17
32847_at U48959 myosin, light polypeptide kinase 0.5 0.0 -0.3 -0.2 0.000 0.926 0.028 0.402 HD+18
39829_at AB016811 ADP-ribosylation factor-like 7 0.5 0.1 -0.4 -0.3 0.002 0.457 0.035 0.049 HD+19
757_at D28364 annexin II, 5 UTR 0.5 -0.2 -0.2 -0.4 0.000 0.313 0.367 0.007 HD+20
40362_at X61498 nuclear factor of light polypeptide gene enhancer 0.5 -0.3 -0.2 -0.2 0.000 0.096 0.476 0.125 HD+21
33501_r_at S71043 Ig alpha 2=immunoglobulin A heavy chain allotype 2 0.5 -0.1 -0.3 -0.2 0.000 0.512 0.022 0.211 HD+22
33284_at M19507 myeloperoxidase 0.5 -0.3 -0.4 0.0 0.001 0.069 0.006 0.697 HD+23
34546_at AI250799 defensin, alpha 4, corticostatin 0.5 -0.1 -0.3 -0.2 0.000 0.406 0.052 0.205 HD+24
40155_at D31883 actin binding LIM protein 1 0.5 0.0 -0.3 -0.3 0.000 0.895 0.027 0.087 HD+25
38805_at X89750 TGFB-induced factor (TALE family homeobox) -0.8 0.2 0.3 0.3 0.000 0.395 0.003 0.402 HD-01
39286_at D64109 transducer of ERBB2, 2 -0.6 0.2 0.2 0.5 0.000 0.218 0.154 0.021 HD-02
36628_at L42542 ralA binding protein 1 -0.6 0.2 0.2 0.4 0.001 0.312 0.166 0.031 HD-03
34402_at AB024327 unr-interacting protein -0.6 0.2 0.2 0.3 0.000 0.213 0.044 0.247 HD-04
33893_r_at AB007939 KIAA0470 gene product -0.6 -0.1 0.4 0.3 0.000 0.569 0.004 0.117 HD-05
39024_at AF042357 nucleoporin 98kD -0.5 0.1 0.3 0.3 0.001 0.713 0.095 0.063 HD-06
41549_s_at AF091077 adaptor-related protein complex 1, sigma 2 subunit -0.5 0.6 0.2 -0.1 0.000 0.000 0.356 0.498 HD-07
41360_at AA044787 CCR4-NOT transcription complex, subunit 8 -0.5 0.1 0.1 0.4 0.000 0.584 0.290 0.035 HD-08
37781_at AB023138 neurexin 2 -0.5 0.6 0.1 0.2 0.000 0.002 0.528 0.243 HD-09
37642_at D63877 KIAA0157 protein -0.5 -0.1 0.3 0.4 0.000 0.514 0.034 0.017 HD-10
41598_at AA890010 clone=IMAGE-1403679 -0.5 0.3 0.3 0.1 0.001 0.109 0.013 0.894 HD-11
38270_at AF005043 poly (ADP-ribose) glycohydrolase -0.5 0.2 0.3 0.2 0.001 0.364 0.014 0.719 HD-12
41597_s_at AF047442 SEC22 vesicle trafficking protein-like 1 -0.5 0.3 0.3 0.2 0.000 0.180 0.079 0.427 HD-13
34751_at AI970189 KIAA0997 protein -0.5 0.5 0.2 0.0 0.002 0.008 0.100 0.747 HD-14
37902_at L13278 crystallin, zeta (quinone reductase) -0.5 0.1 0.4 0.1 0.000 0.474 0.015 0.785 HD-15
36585_at M36341 ADP-ribosylation factor 4 -0.5 0.0 0.3 0.2 0.000 0.784 0.051 0.151 HD-16
38973_at AB028943 HIC1-related gene on chromosome 22 -0.5 0.2 0.1 0.3 0.000 0.277 0.129 0.173 HD-17
38093_at U90909 clone 23722 mRNA -0.5 0.1 0.4 0.1 0.000 0.712 0.027 0.249 HD-18
31510_s_at Z48950 H3 histone, family 3B (H3.3B) -0.5 0.2 0.2 0.3 0.000 0.149 0.131 0.148 HD-19
40976_at AF052432 katanin p80 (WD40-containing) subunit B 1 -0.5 0.1 0.1 0.3 0.000 0.595 0.247 0.076 HD-20
37984_s_at M57763 ADP-ribosylation factor 6 -0.5 0.2 0.2 0.3 0.000 0.200 0.186 0.137 HD-21
39436_at AF079221 BCL2/adenovirus E1B 19kD interacting protein -0.5 0.5 0.1 0.2 0.000 0.012 0.753 0.148 HD-22
1512_at D86550 tyrosine-(Y)-phosphorylation regulated kinase -0.5 0.0 0.4 0.1 0.001 0.965 0.002 0.654 HD-23
38994_at AF037989 STAT induced STAT inhibitor-2 -0.5 0.3 0.3 0.0 0.000 0.098 0.093 0.732 HD-24
41790_at AL031230 glycosylphosphatidylinositol specific phospholipase -0.5 0.2 0.3 0.0 0.001 0.213 0.005 0.829 HD-25
322_at D88532 phosphoinositide-3-kinase, regulatory subunit -0.3 0.8 -0.1 0.0 0.050 0.000 0.359 0.897 HDMP+01
39951_at L20826 plastin 1 (I isoform) -0.2 0.8 0.0 -0.2 0.112 0.000 0.878 0.173 HDMP+02
32257_f_at AF003001 telomeric repeat binding factor (NIMA-interacting) 1 -0.2 0.7 0.0 -0.1 0.188 0.000 0.652 0.522 HDMP+03
782_at U93867 polymerase (RNA) III (DNA directed) (62kD) -0.1 0.7 -0.1 -0.4 0.492 0.000 0.436 0.060 HDMP+04
491_at U46116 protein tyrosine phosphatase, receptor type, G 0.0 0.6 -0.2 -0.4 0.914 0.001 0.181 0.080 HDMP+05
37563_at AB007871 KIAA0411 gene product -0.1 0.6 -0.1 -0.2 0.641 0.001 0.757 0.086 HDMP+06
40478_at AL021396 hypothetical protein -0.1 0.6 -0.1 -0.2 0.462 0.000 0.311 0.380 HDMP+07
39489_g_at W27720 protocadherin 9 -0.2 0.6 -0.1 0.0 0.082 0.001 0.588 0.825 HDMP+08
39008_at M13699 ceruloplasmin (ferroxidase) -0.1 0.6 -0.3 0.1 0.586 0.001 0.028 0.603 HDMP+09
36729_g_at M76446 adrenergic, alpha-1D-, receptor -0.1 0.6 -0.1 -0.2 0.614 0.002 0.607 0.182 HDMP+10
40383_at AB023200 gene from NF2/meningioma region of 22q12 0.0 0.6 -0.2 -0.2 0.895 0.002 0.083 0.404 HDMP+11
1368_at M27492 interleukin 1 receptor, type I -0.1 0.6 -0.1 -0.2 0.529 0.001 0.298 0.449 HDMP+12
33353_at W26466 32f11 Homo sapiens cDNA 0.1 0.6 -0.4 -0.1 0.330 0.002 0.005 0.573 HDMP+13
35002_g_at Z85986 serine/threonine kinase 38 -0.4 0.6 -0.1 0.3 0.002 0.002 0.652 0.194 HDMP+14
34102_at M90424 lipocalin 1 -0.1 0.6 -0.3 0.1 0.336 0.001 0.036 0.531 HDMP+15
36435_at AF070670 protein phosphatase 1A -0.1 0.6 -0.2 0.0 0.370 0.006 0.286 0.806 HDMP+16
39943_at U27459 origin recognition complex, subunit 2-like -0.3 0.6 -0.2 0.2 0.013 0.001 0.202 0.267 HDMP+17
39544_at AB002351 desmuslin -0.3 0.6 -0.1 0.2 0.030 0.001 0.255 0.089 HDMP+18
33432_at AI547308 similar to hypothetical protein MNCb-2386 -0.1 0.6 -0.3 0.0 0.511 0.006 0.028 0.856 HDMP+19
37583_at U52191 Smcy homolog, Y chromosome (mouse) -0.2 0.5 0.1 -0.3 0.172 0.001 0.377 0.050 HDMP+20
33427_s_at AF106861 attractin -0.1 0.5 -0.1 -0.1 0.276 0.002 0.610 0.600 HDMP+21
32443_at U28687 zinc finger protein 157 (HZF22) -0.3 0.5 -0.1 0.0 0.062 0.007 0.493 0.981 HDMP+22
31896_at AL050281 neuroblastoma-amplified protein -0.2 0.5 -0.1 0.0 0.146 0.007 0.366 0.984 HDMP+23
34594_at D13644 related to the N terminus of tre -0.4 0.5 0.2 -0.1 0.005 0.002 0.643 0.872 HDMP+24
35308_at D83200 hypothetical protein MGC2668 -0.4 0.5 -0.1 0.1 0.009 0.003 0.341 0.327 HDMP+25
41667_s_at AJ006068 dTDP-D-glucose 4,6-dehydratase -0.1 -0.7 0.2 0.3 0.313 0.000 0.063 0.137 HDMP-01
37662_at AI701164 ubiquitin-conjugating enzyme E2G 1 -0.1 -0.6 0.3 0.2 0.281 0.000 0.058 0.135 HDMP-02
38713_at Z99716 septin 3 0.5 -0.6 0.0 -0.1 0.000 0.002 0.714 0.786 HDMP-03
32117_at U51698 apoptosis antagonizing transcription factor 0.0 -0.6 0.3 0.1 0.823 0.004 0.070 0.378 HDMP-04
36514_at U66469 cell growth regulatory with ring finger domain 0.3 -0.6 -0.1 0.1 0.026 0.002 0.572 0.614 HDMP-05
38313_at AB028985 ATP-binding cassette, sub-family A (ABC1) 0.2 -0.6 0.3 -0.2 0.121 0.003 0.084 0.272 HDMP-06
39307_s_at X81637 clathrin light chain b gene 0.0 -0.6 0.3 0.1 0.781 0.002 0.029 0.906 HDMP-07
41826_at W28287 KIAA1467 protein 0.1 -0.6 0.2 0.1 0.592 0.001 0.345 0.360 HDMP-08
37130_g_at AI936758 neuropeptide FF-amide peptide precursor 0.2 -0.5 0.3 -0.1 0.208 0.006 0.247 0.901 HDMP-09
38082_at AB014550 KIAA0650 protein -0.1 -0.5 0.2 0.4 0.377 0.000 0.161 0.010 HDMP-10
34960_g_at M15059 Fc fragment of IgE, low affinity II 0.1 -0.5 0.1 0.1 0.299 0.002 0.500 0.458 HDMP-11
37121_at S69115 natural killer cell group 7 sequence 0.3 -0.5 0.1 -0.2 0.018 0.005 0.571 0.389 HDMP-12
37244_at AA746355 ubiquitin carboxyl-terminal esterase L3 0.2 -0.5 -0.2 0.4 0.112 0.004 0.502 0.056 HDMP-13
1814_at D50683 transforming growth factor, beta receptor II -0.1 -0.5 0.1 0.4 0.351 0.003 0.211 0.160 HDMP-14
579_at M95724 centromere protein C 1 0.3 -0.5 -0.1 0.1 0.035 0.007 0.671 0.670 HDMP-15
35969_at N23137 M-phase phosphoprotein 9 0.0 -0.5 0.2 0.2 0.954 0.002 0.226 0.213 HDMP-16
33706_at AB006198 squamous cell carcinoma antigen 0.1 -0.5 0.1 0.2 0.656 0.005 0.261 0.245 HDMP-17
41246_at AI743134 trinucleotide repeat containing 3 0.1 -0.5 0.0 0.3 0.357 0.003 0.956 0.099 HDMP-18
31838_at U79274 protein predicted by clone 23733 0.2 -0.5 0.1 0.0 0.196 0.004 0.583 0.854 HDMP-19
35963_at AI201243 HLA class II region expressed gene KE2 0.2 -0.5 -0.1 0.2 0.071 0.004 0.982 0.717 HDMP-20
41398_at AL049305 hypothetical protein FLJ21940 0.1 -0.5 0.1 0.0 0.301 0.003 0.510 0.940 HDMP-21
40821_at M61832 S-adenosylhomocysteine hydrolase 0.1 -0.5 0.0 0.2 0.392 0.002 0.499 0.670 HDMP-22
41277_at AW021542 sin3-associated polypeptide, 18kD 0.0 -0.5 0.3 0.0 0.862 0.004 0.103 0.716 HDMP-23
33870_at AB029005 chromosome 5 open reading frame 7 -0.1 -0.5 0.3 0.3 0.324 0.005 0.053 0.155 HDMP-24
32102_at AB018273 spastic ataxia of Charlevoix-Saguenay (sacsin) -0.1 -0.5 0.3 0.2 0.635 0.005 0.021 0.538 HDMP-25
38041_at U41514 UDP-N-acetyl-alpha-D-galactosamine -0.2 -0.2 0.5 -0.2 0.167 0.241 0.002 0.246 LDMP+01
32695_at Z97632 bombesin-like receptor 3 -0.1 -0.3 0.5 -0.1 0.502 0.058 0.001 0.340 LDMP+02
40377_at AB014582 KIAA0682 gene product -0.3 -0.1 0.5 -0.1 0.044 0.720 0.000 0.270 LDMP+03
37036_at AB002299 KIAA0301 protein -0.2 -0.3 0.5 -0.1 0.246 0.102 0.012 0.899 LDMP+04
39717_g_at AI597616 mitochondrial ribosomal protein L33 -0.4 -0.1 0.5 0.1 0.001 0.429 0.005 0.428 LDMP+05
33773_at U13948 myeloid/lymphoid or mixed-lineage leukemia -0.2 0.0 0.5 -0.3 0.087 0.881 0.007 0.127 LDMP+06
40030_at Y15801 protein kinase, Y-linked -0.1 -0.4 0.5 -0.1 0.541 0.022 0.000 0.169 LDMP+07
891_at M77698 YY1 transcription factor -0.5 -0.1 0.5 0.1 0.002 0.532 0.000 0.738 LDMP+08
34307_at U81006 transmembrane 9 superfamily member 2 -0.2 -0.3 0.5 -0.1 0.120 0.136 0.000 0.568 LDMP+09
32643_at L07956 glucan (1,4-alpha-), branching enzyme 1 -0.1 -0.2 0.5 -0.2 0.412 0.227 0.025 0.539 LDMP+10
40473_at AF024636 serine/threonine kinase 24 (STE20 homolog, yeast) -0.5 -0.1 0.5 0.1 0.000 0.770 0.002 0.431 LDMP+11
39490_f_at W26381 ADP-ribosylation factor GTPase activating protein 1 -0.3 0.0 0.5 -0.1 0.030 0.961 0.002 0.414 LDMP+12
38472_at D63477 KIAA0143 protein 0.0 -0.2 0.5 -0.3 0.815 0.332 0.003 0.064 LDMP+13
1914_at U66838 cyclin A1 -0.1 0.0 0.5 -0.3 0.560 0.793 0.074 0.323 LDMP+14
38042_at X03674 glucose-6-phosphate dehydrogenase -0.1 0.1 0.5 -0.5 0.617 0.524 0.001 0.002 LDMP+15
34891_at AI540958 dynein, cytoplasmic, light polypeptide -0.4 0.1 0.5 0.0 0.004 0.715 0.000 0.693 LDMP+16
33457_at AB029028 KIAA1105 protein -0.1 -0.3 0.5 -0.2 0.551 0.125 0.003 0.169 LDMP+17
37497_at L16499 hematopoietically expressed homeobox -0.4 0.2 0.5 0.0 0.000 0.339 0.026 0.685 LDMP+18
41750_at D49489 protein disulfide isomerase-related protein -0.2 -0.2 0.4 -0.1 0.221 0.245 0.001 0.316 LDMP+19
37735_at U31383 guanine nucleotide binding protein 10 -0.2 -0.3 0.4 0.1 0.081 0.058 0.000 0.597 LDMP+20
316_g_at D45132 PR domain containing 2, with ZNF domain -0.1 -0.2 0.4 -0.3 0.468 0.347 0.011 0.211 LDMP+21
2044_s_at M15400 retinoblastoma 1 (including osteosarcoma) -0.2 -0.3 0.4 0.0 0.162 0.082 0.012 0.697 LDMP+22
41562_at L13689 murine leukemia viral (bmi-1) oncogene homolog -0.3 -0.1 0.4 0.0 0.071 0.430 0.000 0.160 LDMP+23
40167_s_at AF038187 CS box-containing WD protein -0.1 -0.3 0.4 -0.1 0.626 0.055 0.002 0.568 LDMP+24
40607_at U97105 dihydropyrimidinase-like 2 -0.1 -0.2 0.4 -0.2 0.564 0.304 0.005 0.179 LDMP+25
37096_at M34379 elastase 2, neutrophil 0.6 0.0 -0.5 -0.2 0.000 0.811 0.000 0.279 LDMP-01
37391_at X12451 cathepsin L 0.1 0.2 -0.5 0.2 0.396 0.164 0.000 0.320 LDMP-02
31914_at AF054177 chromodomain helicase DNA binding protein 1-like 0.3 0.4 -0.5 -0.2 0.063 0.015 0.001 0.274 LDMP-03
1186_at D49493 growth differentiation factor 10 0.1 0.2 -0.5 0.2 0.284 0.306 0.006 0.436 LDMP-04
34967_at AF001549 RNA polymerase I transcription factor RRN3 0.0 0.2 -0.5 0.4 0.966 0.328 0.004 0.052 LDMP-05
34243_i_at U89358 lethal (3) malignant brain tumor l(3)mbt protein 0.4 0.1 -0.5 0.0 0.009 0.696 0.003 0.846 LDMP-06
39948_at AI693307 MAX protein 0.3 0.0 -0.5 0.1 0.029 0.824 0.010 0.998 LDMP-07
41218_at AB018272 KIAA0729 protein -0.1 0.3 -0.5 0.4 0.385 0.111 0.002 0.009 LDMP-08
2081_s_at L07032 protein kinase C, theta 0.1 0.3 -0.5 0.2 0.377 0.122 0.002 0.398 LDMP-09
34472_at AB012911 frizzled homolog 6 (Drosophila) 0.5 -0.2 -0.5 0.0 0.000 0.302 0.001 0.877 LDMP-10
38879_at D83664 S100 calcium binding protein A12 (calgranulin C) 0.5 0.0 -0.5 -0.2 0.000 0.936 0.008 0.145 LDMP-11
39369_at AB023152 KIAA0935 protein 0.3 0.0 -0.4 0.0 0.025 0.835 0.007 0.742 LDMP-12
32821_at AI762213 lipocalin 2 (oncogene 24p3) 0.6 -0.1 -0.4 -0.2 0.000 0.579 0.002 0.296 LDMP-13
35023_at U00803 fyn-related kinase 0.0 0.3 -0.4 0.1 0.846 0.077 0.012 0.471 LDMP-14
37927_at X12654 chromosome condensation 1 0.3 -0.3 -0.4 0.3 0.069 0.105 0.006 0.048 LDMP-15
39993_at D11466 phosphatidylinositol glycan, class A 0.2 0.1 -0.4 0.2 0.131 0.729 0.002 0.326 LDMP-16
795_s_at X66358 cyclin-dependent kinase-like 1 (CDC2-related kinase) 0.1 0.2 -0.4 0.2 0.460 0.244 0.000 0.162 LDMP-17
40684_at U78190 GTP cyclohydrolase I feedback regulatory protein 0.3 0.1 -0.4 0.0 0.040 0.548 0.003 0.920 LDMP-18
39919_at AI423340 C1q-related factor -0.1 0.4 -0.4 0.4 0.417 0.056 0.022 0.044 LDMP-19
39956_at AF041853 kinesin family member 3A 0.1 0.0 -0.4 0.4 0.340 0.966 0.007 0.042 LDMP-20
41232_at AL050022 DKFZP564D116 protein 0.2 0.0 -0.4 0.3 0.210 0.993 0.005 0.117 LDMP-21
32869_at AF073362 MRE11 meiotic recombination 11 homolog A -0.1 0.4 -0.4 0.3 0.414 0.035 0.007 0.041 LDMP-22
39201_r_at W28760 51c8 Homo sapiens cDNA 0.2 0.3 -0.4 -0.1 0.115 0.146 0.001 0.910 LDMP-23
39527_at AF090102 KIAA1155 protein 0.3 0.0 -0.4 0.1 0.037 0.879 0.004 0.706 LDMP-24
36105_at M18728 carcinoembryonic antigen-related cell adhesion 0.4 0.0 -0.4 -0.2 0.002 0.897 0.003 0.538 LDMP-25
41415_at L36720 bystin-like -0.3 -0.2 0.0 0.6 0.020 0.242 0.973 0.000 Mp+01
36225_s_at W27611 splicing factor proline/glutamine rich -0.4 0.1 0.0 0.6 0.005 0.495 0.751 0.003 Mp+02
35005_at AF051941 nucleoside diphosphate kinase type 6 -0.2 -0.2 -0.2 0.6 0.100 0.354 0.205 0.000 Mp+03
40690_at X54942 CDC28 protein kinase 2 -0.3 -0.2 0.1 0.6 0.014 0.296 0.274 0.003 Mp+04
39643_at U94703 polymerase (DNA directed), gamma 2 -0.1 -0.1 -0.2 0.6 0.346 0.683 0.241 0.001 Mp+05
35943_s_at D13317 GA binding protein transcription factor -0.1 -0.1 -0.2 0.5 0.416 0.522 0.242 0.000 Mp+06
39637_at U14528 solute carrier family 26 (sulfate transporter) -0.2 -0.2 -0.1 0.5 0.155 0.277 0.721 0.000 Mp+07
41462_at AF065482 sorting nexin 2 -0.2 -0.4 0.1 0.5 0.063 0.028 0.171 0.008 Mp+08
1199_at D13748 eukaryotic translation initiation factor 4A, isoform 1 -0.2 -0.1 -0.1 0.5 0.279 0.635 0.587 0.006 Mp+09
39368_at AL031668 eukaryotic translation initiation factor 2 -0.3 -0.1 0.1 0.5 0.022 0.448 0.265 0.017 Mp+10
40349_at AL049442 clone DKFZp586N1720 -0.3 -0.1 -0.1 0.5 0.039 0.581 0.657 0.000 Mp+11
32251_at AA149307 hypothetical protein FLJ21174 -0.4 0.0 -0.1 0.5 0.003 0.793 0.287 0.000 Mp+12
40191_s_at AI761647 clone=IMAGE-2370113 -0.5 0.3 -0.3 0.5 0.000 0.084 0.262 0.007 Mp+13
1939_at M22898 tumor protein p53 (Li-Fraumeni syndrome) -0.2 -0.2 -0.1 0.5 0.093 0.262 0.936 0.008 Mp+14
35432_at AF074723 RNA polymerase II transcriptional regulation mediator -0.1 -0.3 0.0 0.5 0.333 0.103 0.636 0.011 Mp+15
2025_s_at M80261 APEX nuclease (multifunctional DNA repair enzyme) -0.1 -0.1 -0.1 0.5 0.331 0.531 0.649 0.010 Mp+16
37535_at M27691 cAMP responsive element binding protein 1 -0.3 0.1 -0.1 0.5 0.062 0.490 0.515 0.006 Mp+17
37722_s_at U26266 deoxyhypusine synthase -0.3 -0.1 0.0 0.5 0.013 0.718 0.835 0.004 Mp+18
40122_at AF037448 NS1-associated protein 1 -0.2 -0.1 -0.1 0.5 0.124 0.551 0.979 0.011 Mp+19
1936_s_at M13930 v-myc myelocytomatosis viral oncogene homolog -0.5 0.2 0.0 0.5 0.001 0.292 0.827 0.001 Mp+20
1944_f_at AF001359 mutL homolog 1, colon cancer, nonpolyposis type 2 0.0 -0.4 -0.1 0.5 0.980 0.013 0.789 0.012 Mp+21
628_at L37882 frizzled homolog 2 (Drosophila) -0.1 -0.3 0.0 0.5 0.449 0.077 0.979 0.003 Mp+22
38414_at U05340 CDC20 cell division cycle 20 homolog -0.1 -0.3 0.0 0.5 0.635 0.087 0.895 0.007 Mp+23
39731_at Z23064 RNA binding motif protein, X chromosome -0.4 -0.1 0.2 0.5 0.003 0.626 0.123 0.011 Mp+24
32129_at AL079314 hypothetical protein, similar to PRAJA1 -0.1 -0.1 -0.2 0.5 0.459 0.505 0.354 0.008 Mp+25
35227_at U72066 retinoblastoma binding protein 8 0.1 0.1 0.4 -0.8 0.370 0.659 0.063 0.001 MP-01
39775_at X54486 serine (or cysteine) proteinase inhibitor, clade G 0.2 0.0 0.4 -0.7 0.184 0.796 0.021 0.000 MP-02
38386_r_at U34683 glutathione synthetase 0.4 0.1 0.0 -0.7 0.001 0.684 0.820 0.000 MP-03
39957_at AF150247 hypothetical protein 0.2 -0.2 0.3 -0.6 0.103 0.293 0.108 0.000 MP-04
1106_s_at M12959 T cell receptor alpha locus 0.4 -0.1 0.1 -0.6 0.014 0.703 0.535 0.000 MP-05
39230_at AL022318 similar to APOBEC1 0.3 0.0 0.2 -0.6 0.053 0.999 0.436 0.001 MP-06
40755_at X92841 MHC class I polypeptide-related sequence A 0.4 -0.2 0.1 -0.6 0.003 0.238 0.517 0.001 MP-07
32904_at M28393 perforin 1 (pore forming protein) 0.2 0.1 0.2 -0.6 0.217 0.634 0.177 0.002 MP-08
34660_at AI142565 ribonuclease, RNase A family, k6 0.3 0.2 -0.1 -0.6 0.029 0.319 0.382 0.004 MP-09
41188_at W28186 putative integral membrane transporter 0.1 0.0 0.3 -0.6 0.588 0.807 0.038 0.003 MP-10
35621_at L77213 phosphomevalonate kinase 0.6 -0.2 0.0 -0.6 0.000 0.158 0.810 0.004 MP-11
37980_at U03644 CBF1 interacting corepressor 0.1 0.1 0.2 -0.5 0.378 0.572 0.374 0.002 MP-12
41855_at AF030424 histone acetyltransferase 1 0.1 -0.1 0.4 -0.5 0.559 0.638 0.018 0.000 MP-13
35109_at AB018299 KIAA0756 protein 0.2 -0.1 0.2 -0.5 0.106 0.745 0.289 0.008 MP-14
37624_at M29458 carbonic anhydrase III, muscle specific 0.2 0.2 0.0 -0.5 0.231 0.329 0.864 0.001 MP-15
40942_g_at W27026 VAMP (vesicle-associated membrane protein) 0.0 0.3 0.2 -0.5 0.869 0.059 0.494 0.009 MP-16
37967_at AF000424 lymphocyte antigen 117 0.3 -0.1 0.1 -0.5 0.040 0.477 0.780 0.003 MP-17
36155_at D87465 KIAA0275 gene product 0.3 0.3 -0.2 -0.5 0.022 0.164 0.185 0.001 MP-18
31556_at X61072 T cell receptor, clone IGRA17 0.3 0.0 0.1 -0.5 0.078 0.799 0.612 0.014 MP-19
32140_at Y08110 sortilin-related receptor 0.4 0.2 0.0 -0.5 0.006 0.345 0.723 0.003 MP-20
36710_at Z38026 cathelicidin antimicrobial peptide 0.5 -0.1 -0.2 -0.5 0.001 0.622 0.076 0.031 MP-21
41400_at K02581 thymidine kinase 1, soluble 0.2 0.1 0.1 -0.5 0.150 0.777 0.632 0.005 MP-22
40141_at AB014595 cullin 4B 0.0 0.4 0.1 -0.5 0.931 0.019 0.653 0.003 MP-23
38968_at AB005047 SH3-domain binding protein 5 0.1 0.1 0.2 -0.5 0.591 0.523 0.200 0.004 MP-24
34965_at AF031824 cystatin F (leukocystatin) 0.4 -0.1 0.0 -0.5 0.003 0.462 0.605 0.018 MP-25

Figure 5: Treatment-induced changes in percentage of ALL cells in S-phase.

Figure 5: Treatment-induced changes in percentage of ALL cells in S-phase.

Treatment-induced changes in percentage of ALL cells in S-phase of the cell cycle. Percentages of bone marrow leukemia cells in S-phase from bone marrow leukemia blast at diagnosis and post-treatment were available for 23 of the 60 patients analyzed in this study. Propidium-iodide stained DNA content was measured by flow cytometry with the Coulter EPICS-V flow cytometer (Coulter Electronics. Inc., Hialeah, Florida). The computer program PEAK was used to calculate the percentages of cells in the G0/G1, S, G2+M phase. (a) The median fold-change of ATM expression in the four treatment groups: HDMTX, n=7, median= +2.3, range (-1.2 to 3.2); MP, n=6, median= +1.3, range (-3.0 to 2.6); HDMTX+MP, n=5, median= -1.1, range (-2.3 to 1.3); LDMTX+MP, n=5, median= -1.1, range (-2.0 to 1.3). ATM induction was significantly greater after HDMTX as compared to the other three treatments (P=0.007, Wilcoxon). (b) The median change in %S-phase of ALL cells from pre- to post-treatment in the four treatment groups: HDMTX, median= -35, range (-67 to102); MP, median= +13.6, range (-27 to 95); HDMTX+MP, median= +87, range (-88 to 386); LDMTX+MP, median= +105, range (-38 to187). The difference in change of %S-phase was statistically significant when the HDMTX group was compared to the other three treatments combined (P=0.033, Wilcoxon).