Table 1 Clinical characteristics of MDS patients and expression of signal pathway protein in MDS CD34+ cells

From: Rigosertib as a selective anti-tumor agent can ameliorate multiple dysregulated signaling transduction pathways in high-grade myelodysplastic syndrome

       

#Relative expression (fold change, MDS/Normal controls)

No.

Sex

Age

Diagnosis*

IPSS-R

Karyotype

Rigosertib, (&LD50, 24 h, μmol/L)

Akt1

p-Akt1

p-p38

p-ERK1/2

p-JNK

p-STAT1

p-STAT3

p-β-catenin

p-GSK 3α/β

p-p53

P1

M

76

RARS

4.5

Del(11q)

25.6

0.91

0.91

2.14

2.33

3.10

0.54

1.19

0.91

1.61

1.76

P2

M

56

MDS-U

1.5

Normal

NA*

1.23

0.77

2.50

2.00

3.53

0.89

1.40

0.96

0.91

1.88

P3

F

62

RCMD

2.5

Normal

18.5

0.84

1.15

1.50

2.01

1.29

NA

0.81

NA

NA

NA

P4

M

45

RCMD

5

Trisomy 8

NA

1.35

1.49

2.07

1.57

3.02

1.25

0.97

1.68

1.71

0.99

P5

F

40

RCMD

2

Normal

NA

0.76

0.58

1.00

1.12

3.10

2.32

0.65

1.01

2.32

1.65

P6

M

81

RCMD

6

Trisomy 8

NA

1.93

1.78

1.29

1.19

2.16

1.79

2.21

2.21

2.52

1.10

P7

M

60

RCMD

6

t(5;11), del(17p)

NA

1.66

1.78

1.79

0.84

2.59

1.61

1.94

1.83

2.21

1.32

P8

M

29

RCMD

4

Trisomy 8

NA

1.05

1.34

2.14

0.60

2.41

1.52

1.08

1.11

1.51

1.43

P9

M

57

RCMD

3

Del(7q)

NA

1.10

0.91

1.43

2.58

2.41

1.34

0.81

0.77

0.40

0.77

P10

F

58

RCMD

3.5

Trisomy 8

14.2

1.53

2.06

2.36

0.77

3.45

0.71

0.70

1.54

1.21

1.54

P11

M

52

RCMD

7

5q-,-7,-13,-18

NA

2.47

2.21

1.14

0.87

1.81

0.54

1.67

1.63

1.91

1.43

P12

M

72

RCMD

3.5

Normal

NA

0.85

1.49

2.86

1.35

4.14

0.80

1.40

1.30

1.01

1.21

P13

M

78

RCMD

5

del(5q), inv(9)

NA

2.12

1.97

1.71

2.92

1.03

1.07

1.57

0.87

0.81

1.32

P14

M

79

RCMD

5

-5,-16,-18,-20

8.6

2.26

1.63

1.79

0.58

0.78

NA

2.05

1.97

0.70

0.88

P15

F

53

RCMD

4

Normal

28.1

0.87

1.25

1.86

0.97

NA

0.45

NA

1.44

0.50

2.21

P16

F

64

RCMD

4.5

-X, tri3, t(7;11)

7.4

1.66

2.40

1.79

0.77

0.60

1.16

0.27

1.20

1.21

0.88

P17

M

53

RCMD

4.5

Normal

10.7

2.08

2.16

0.93

0.87

NA

0.45

NA

1.73

NA

NA

P18

M

60

RAEB-1

4

Normal

10.4

2.05

2.16

1.50

2.28

1.90

0.71

2.27

1.11

2.01

0.47

P19

F

64

RAEB-1

7.5

-7

NA

2.57

3.31

1.14

0.87

1.38

0.80

2.10

1.59

1.71

0.65

P20

F

62

RAEB-1

6

Del(9q),Del(20q)

NA

3.16

3.55

2.29

1.26

2.67

0.89

0.65

0.96

2.32

0.54

P21

M

68

RAEB-1

8.5

-3, del(5q), -6

7.1

2.33

2.69

1.64

1.16

0.69

1.61

2.21

1.63

1.41

0.76

P22

M

70

RAEB-1

4.5

Trisomy 8

NA

1.62

2.21

2.21

1.06

1.38

1.43

3.45

1.78

1.71

0.55

P23

F

59

RAEB-1

5

Normal

NA

2.94

2.45

1.29

1.83

2.07

1.34

1.89

1.68

3.52

0.44

P24

M

61

RAEB-1

4.5

Normal

NA

1.72

1.82

3.00

1.35

1.21

0.71

1.08

1.49

2.11

1.10

P26

F

40

RAEB-1

6

Trisomy 8

NA

2.04

1.68

1.79

1.16

1.38

1.43

1.13

1.35

2.82

1.54

P25

M

68

RAEB-2

9

Der(3;5), -6, tri8

NA

2.28

2.97

0.79

0.97

1.64

1.07

2.43

1.73

3.02

0.89

P27

F

50

RAEB-2

5.5

normal

12.6

1.56

2.25

1.79

2.43

NA

0.71

0.65

1.63

0.50

0.99

P28

F

39

RAEB-2

5.5

Normal

7.5

2.71

2.59

1.21

0.58

2.59

0.98

1.78

1.83

2.42

0.75

P29

F

64

RAEB-2

5.5

Normal

NA

3.24

3.12

2.14

3.44

2.50

1.16

1.94

1.54

3.22

1.21

P30

M

50

RAEB-2

4

Normal

5.6

2.36

2.30

1.29

1.57

NA

1.61

1.89

1.68

2.52

0.86

P31

F

61

RAEB-2

6

Del(5q)

10.2

2.11

2.25

0.71

0.58

1.38

1.79

1.35

1.49

3.12

0.73

P32

F

70

RAEB-2

5.5

Normal

8.6

2.48

2.59

0.36

2.93

1.38

1.96

1.19

1.30

0.81

1.32

P33

F

34

RAEB-2

7.5

Trisomy 8

6.4

1.79

1.78

0.64

0.77

NA

1.34

1.51

2.16

1.31

0.63

P34

M

47

RAEB-2

6

Normal

8.2

3.12

2.78

1.07

0.39

1.90

1.07

2.05

1.92

3.22

0.76

P35

M

62

RAEB-2

5.5

Normal

NA

2.65

2.49

1.43

0.48

2.67

1.52

2.00

0.87

1.71

0.97

  1. *Morphologic diagnosis at presentation in MDS according to WHO classification. RA, refractory anemia; RCMD, refractory cytopenia with multilineage dysplasia; RAEB-1/2, refractory anemia with excess blasts 1/2.
  2. F, female; M, male. IPSS-R, revised international prognostic scoring system. NA, not available.
  3. &In order to assess the LD50, CD34+ cells and cell lines were exposed to increasing concentrations of rigosertib ranging from 0.5 μmol/L to 20 μmol/L for 24 hours. The LD50 value was obtained by calculating the percentage of CD34+ cells stained with Annexin V in each sample at 24 hours
  4. #The expression or phosphorylation of signal pathway proteins in CD34+ cells was quantified by flow cytometry based on the mean fluorescence intensity (MFI). The relative expression was represented in the ratio of MFI (MDS: Normal control). p-Akt1, phosphorylated Akt1.
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