Table 1. Clinical characteristics of MDS patients and expression of signal pathway protein in MDS CD34+ cells.
| #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 |
*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.
F, female; M, male. IPSS-R, revised international prognostic scoring system. NA, not available.
&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
#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.