Background
Methods
Patients
Characteristics | Number (%) |
---|---|
Gender (Male/female) | 37: 21 |
Median age (year, range) | 69 (18–86) |
Age (years) | |
<60 | 22 (37.9) |
≥60 | 36 (62.1) |
Complete blood count at bone marrow sample collection | |
White blood cell (103/μL) | 2.6 (0.6–17.2) |
Hemoglobin (g/dL) | 8.0 (4.4–12.2) |
Absolute neutrophil count (/μL) | 1151 (80–11,345) |
Platelet count (103/μL) | 74.5 (3–1029) |
Median bone marrow blast (%, range) | 2.3 (0.0–18.1) |
WHO category | |
RCUD | 12 (20.7) |
RARS | 4 (6.9) |
RCMD | 13 (22.4) |
RAEB | 20 (34.5) |
MDS, U | 9 (15.5) |
IPSS risk groups | |
Low | 8 (13.8) |
Intermediate-1 | 28 (48.3) |
Intermediate-2 | 15 (25.9) |
High | 7 (12.1) |
Revised IPSS | |
Very low | 4 (6.9) |
Low | 14 (24.1) |
Intermediate | 14 (24.1) |
High | 14 (24.1) |
Very High | 12 (20.7) |
Cytogenetic results | |
Karyotype | |
Abnormal karyotype | 32 (55.2) |
Complex karyotype (>3 abnormalities) | 9 (15.5) |
del(5q)/ –5 | 6 (10.5) |
del(7q)/ –7 | 8 (14.0) |
Trisomy 8 | 8 (14.0) |
Abnormal 17p | 3 (5.2) |
del(20q) | 5 (8.8) |
Fluorescence in situ hybridization | |
Abnormal chromosome 1a
| 5 (11.1) |
Abnormal chromosome 5b
| 8 (17.4) |
Abnormal chromosome 7b
| 9 (19.6) |
Abnormal chromosome 8b
| 7 (15.2) |
Abnormal chromosome 20b
| 4 (8.7) |
Karyotyping—Giemsa banding
Interphase fluorescence in situ hybridization for MDS
Telomere quantitative fluorescence in situ hybridization
Targeted sequencing
Statistical analysis
Results
Telomere lengths and clinical profiles
Parameters | Average ± SD |
P value | |
---|---|---|---|
MDS (n = 58) | NC (n = 23) | ||
Age | 63.7 ± 14.6 | 60.9 ± 9.5 | 0.175 |
Gender (M/F) | 37:21 | 16:7 | 0.796 |
No. of cells assessed for telomere lengths | 77.6 ± 38.9 | 98.1 ± 26.3 | 0.004 |
Telomere lengths (T/C ratio) | |||
Minimum | 1.97 ± 1.47 | 4.41 ± 1.36 | <0.001 |
25th percentile (Q1) | 5.49 ± 3.04 | 11.79 ± 3.06 | <0.001 |
Median | 8.56 ± 4.45 | 15.92 ± 3.93 | <0.001 |
Average | 10.08 ± 4.73 | 17.29 ± 4.42 | <0.001 |
Average of 0–10 percentile | 2.95 ± 1.76 | 6.64 ± 1.74 | <0.001 |
Standard Deviation | 6.67 ± 3.01 | 8.07 ± 2.73 | 0.018 |
Cells under the 10th percentile of the NC (%) | 52.1 ± 24.9 |
Multi-gene panel results
Telomere length and genetic mutations/cytogenetic abnormalities
Gene or cytogenetic changes | Number | Mean age |
P value | Telomere lengths (T/C ratio) | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Minimum |
P value | Q1 |
P value | Median |
P value | Average |
P value | Average of 0–10 percentile |
P value | Standard deviation |
P value | Cells under the 10th percentile of normal control (%) |
P value | |||||
Any gene mutation | Mut(+) | 45 | 65.4 ± 12.2 | 0.356 | 2.14 ± 1.53 | 0.043 | 5.82 ± 3.07 | 0.041 | 8.99 ± 4.17 | 0.025 | 10.68 ± 4.56 | 0.014 | 3.18 ± 1.82 | 0.030 | 7.12 ± 2.97 | 0.007 | 48.2 ± 23.6 | 0.017 |
Mut(−) | 13 | 57.9 ± 20.6 | 1.38 ± 1.11 | 4.34 ± 2.80 | 7.12 ± 5.26 | 8.00 ± 4.90 | 2.14 ± 1.32 | 5.13 ± 2.74 | 65.8 ± 25.5 | |||||||||
ASXL1
| Mut(+) | 13 | 65.4 ± 10.8 | 0.837 | 2.13 ± 2.29 | 0.461 | 5.32 ± 3.79 | 0.557 | 8.04 ± 4.83 | 0.595 | 9.39 ± 5.20 | 0.450 | 2.97 ± 2.28 | 0.689 | 5.78 ± 2.40 | 0.310 | 57.4 ± 24.4 | 0.396 |
Mut(−) | 45 | 63.2 ± 15.7 | 1.92 ± 1.17 | 5.54 ± 2.85 | 8.72 ± 4.39 | 10.28 ± 4.63 | 2.94 ± 1.62 | 6.93 ± 3.15 | 50.6 ± 25.1 | |||||||||
CSF3R
| Mut(+) | 3 | 57.3 ± 21.1 | 0.438 | 2.21 ± 0.99 | 0.438 | 7.87 ± 2.87 | 0.087 | 12.43 ± 3.71 | 0.062 | 14.23 ± 4.18 | 0.067 | 3.82 ± 2.29 | 0.459 | 9.23 ± 2.43 | 0.119 | 23.9 ± 13.8 | 0.037 |
Mut(−) | 55 | 64.0 ± 14.4 | 1.96 ± 1.50 | 5.36 ± 3.03 | 8.36 ± 4.42 | 9.86 ± 4.69 | 2.90 ± 1.74 | 6.53 ± 3.00 | 53.7 ± 24.5 | |||||||||
DNMT3A
| Mut(+) | 7 | 72.0 ± 8.9 | 0.117 | 1.66 ± 0.77 | 1.000 | 4.38 ± 1.25 | 0.439 | 6.77 ± 1.58 | 0.425 | 8.14 ± 1.66 | 0.453 | 2.50 ± 0.75 | 0.907 | 5.43 ± 1.88 | 0.779 | 55.6 ± 15.4 | 0.312 |
Mut(−) | 51 | 62.6 ± 15.0 | 2.01 ± 1.55 | 5.65 ± 3.20 | 8.82 ± 4.67 | 10.35 ± 4.96 | 3.01 ± 1.86 | 6.84 ± 3.12 | 51.7 ± 26.0 | |||||||||
EZH2
| Mut(+) | 3 | 71.7 ± 0.6 | 0.240 | 3.95 ± 3.95 | 0.379 | 7.71 ± 5.74 | 0.547 | 10.66 ± 6.28 | 0.525 | 12.57 ± 7.71 | 0.502 | 4.44 ± 3.43 | 0.342 | 7.13 ± 3.97 | 0.869 | 62.3 ± 12.5 | 0.594 |
Mut(−) | 55 | 63.3 ± 14.9 | 1.86 ± 1.22 | 5.37 ± 2.88 | 8.45 ± 4.39 | 9.95 ± 4.59 | 2.87 ± 1.65 | 6.65 ± 3.00 | 51.6 ± 25.4 | |||||||||
IDH2
| Mut(+) | 3 | 66.7 ± 9.1 | 0.843 | 3.08 ± 2.20 | 0.232 | 6.18 ± 4.53 | 0.974 | 10.04 ± 6.42 | 0.715 | 11.70 ± 5.50 | 0.570 | 3.91 ± 2.73 | 0.525 | 8.05 ± 0.99 | 0.232 | 38.7 ± 29.1 | 0.525 |
Mut(−) | 55 | 63.5 ± 14.9 | 1.91 ± 1.43 | 5.46 ± 3.00 | 8.49 ± 4.39 | 9.99 ± 4.73 | 2.90 ± 1.72 | 6.60 ± 3.08 | 52.9 ± 24.8 | |||||||||
NOTCH1
| Mut(+) | 4 | 64.0 ± 17.1 | 0.824 | 2.47 ± 0.84 | 0.189 | 8.01 ± 4.97 | 0.348 | 11.94 ± 7.12 | 0.363 | 14.43 ± 7.72 | 0.236 | 4.24 ± 2.29 | 0.248 | 9.48 ± 3.33 | 0.067 | 35.3 ± 31.7 | 0.332 |
Mut(−) | 54 | 63.7 ± 14.6 | 1.93 ± 1.51 | 5.31 ± 2.84 | 8.32 ± 4.19 | 9.76 ± 4.38 | 2.85 ± 1.71 | 6.46 ± 2.92 | 53.4 ± 24.2 | |||||||||
PLEKHG5
| Mut(+) | 3 | 58.7 ± 10.3 | 0.324 | 1.01 ± 0.52 | 0.158 | 2.86 ± 2.05 | 0.111 | 5.07 ± 2.45 | 0.138 | 6.99 ± 3.37 | 0.291 | 1.57 ± 1.17 | 0.119 | 5.95 ± 2.90 | 0.843 | 70.3 ± 18.0 | 0.193 |
Mut(−) | 55 | 64.0 ± 14.9 | 2.02 ± 1.49 | 5.64 ± 3.04 | 8.76 ± 4.47 | 10.25 ± 4.76 | 3.02 ± 1.77 | 6.71 ± 3.04 | 51.1 ± 25.0 | |||||||||
RUNX1
| Mut(+) | 3 | 56.7 ± 10.6 | 0.193 | 2.13 ± 1.27 | 0.690 | 4.90 ± 1.76 | 0.843 | 10.16 ± 5.47 | 0.641 | 11.73 ± 5.44 | 0.570 | 2.83 ± 0.92 | 0.766 | 8.91 ± 4.08 | 0.193 | 58.0 ± 14.9 | 0.641 |
Mut(−) | 55 | 64.1 ± 14.8 | 1.96 ± 1.49 | 5.53 ± 3.11 | 8.48 ± 4.44 | 9.99 ± 4.73 | 2.95 ± 1.80 | 6.55 ± 2.95 | 51.8 ± 25.4 | |||||||||
SETBP1
| Mut(+) | 3 | 66.7 ± 20.0 | 0.895 | 1.76 ± 0.32 | 0.690 | 4.20 ± 1.02 | 0.547 | 6.48 ± 1.80 | 0.594 | 7.61 ± 2.03 | 0.459 | 2.41 ± 0.43 | 0.869 | 4.76 ± 2.01 | 0.246 | 58.6 ± 18.7 | 0.690 |
Mut(−) | 55 | 63.5 ± 14.5 | 1.98 ± 1.51 | 5.56 ± 3.11 | 8.68 ± 4.54 | 10.22 ± 4.81 | 2.98 ± 1.81 | 6.78 ± 3.04 | 51.8 ± 25.3 | |||||||||
SF3B1
| Mut(+) | 5 | 63.6 ± 11.2 | 0.788 | 2.09 ± 1.60 | 0.872 | 5.13 ± 1.68 | 0.747 | 7.99 ± 2.51 | 0.851 | 9.87 ± 3.23 | 0.768 | 2.72 ± 1.48 | 0.893 | 7.79 ± 3.99 | 0.553 | 47.2 ± 19.2 | 0.517 |
Mut(−) | 53 | 63.7 ± 15.0 | 1.96 ± 1.48 | 5.53 ± 3.16 | 8.62 ± 4.61 | 10.10 ± 4.87 | 2.97 ± 1.80 | 6.57 ± 2.94 | 52.6 ± 25.5 | |||||||||
SRSF2
| Mut(+) | 6 | 73.8 ± 8.0 | 0.101 | 2.40 ± 1.72 | 0.446 | 6.47 ± 3.76 | 0.558 | 10.10 ± 5.48 | 0.446 | 11.42 ± 5.68 | 0.508 | 3.70 ± 2.26 | 0.374 | 6.89 ± 2.55 | 0.737 | 42.4 ± 30.5 | 0.416 |
Mut(−) | 52 | 62.5 ± 14.8 | 1.92 ± 1.45 | 5.38 ± 2.98 | 8.39 ± 4.35 | 9.93 ± 4.65 | 2.86 ± 1.70 | 6.65 ± 3.09 | 53.2 ± 24.3 | |||||||||
TET2
| Mut(+) | 5 | 75.8 ± 6.1 | 0.021 | 2.85 ± 1.69 | 0.131 | 7.06 ± 2.70 | 0.086 | 10.06 ± 2.89 | 0.162 | 12.11 ± 3.22 | 0.138 | 3.91 ± 1.91 | 0.154 | 8.19 ± 3.81 | 0.316 | 33.4 ± 18.5 | 0.076 |
Mut(−) | 53 | 62.6 ± 14.7 | 1.89 ± 1.44 | 5.35 ± 3.06 | 8.43 ± 4.57 | 9.89 ± 4.83 | 2.86 ± 1.74 | 6.53 ± 2.94 | 53.9 ± 24.8 | |||||||||
TP53
| Mut(+) | 8 | 69.0 ± 8.9 | 0.471 | 1.81 ± 1.23 | 0.748 | 5.12 ± 3.06 | 0.974 | 8.44 ± 4.08 | 0.748 | 10.25 ± 4.36 | 0.650 | 2.67 ± 1.84 | 0.471 | 7.62 ± 3.05 | 0.260 | 47.2 ± 27.0 | 0.471 |
Mut(−) | 50 | 62.8 ± 15.3 | 1.99 ± 1.52 | 5.55 ± 3.07 | 8.59 ± 4.55 | 10.05 ± 4.83 | 2.99 ± 1.77 | 6.52 ± 3.01 | 52.9 ± 24.7 | |||||||||
U2AF1
| Mut(+) | 9 | 59.4 ± 12.7 | 0.179 | 2.02 ± 1.01 | 0.408 | 6.62 ± 3.49 | 0.225 | 10.39 ± 5.60 | 0.269 | 12.08 ± 6.35 | 0.318 | 3.49 ± 1.69 | 0.201 | 7.77 ± 4.21 | 0.512 | 47.6 ± 27.7 | 0.614 |
Mut(−) | 49 | 64.5 ± 15.0 | 1.96 ± 1.55 | 5.29 ± 2.95 | 8.23 ± 4.20 | 9.71 ± 4.36 | 2.85 ± 1.78 | 6.47 ± 2.75 | 53.0 ± 24.6 | |||||||||
Karyotype | Normal | 25 | 61.2 ± 15.1 | 0.416 | 2.00 ± 1.95 | 0.237 | 5.32 ± 3.44 | 0.385 | 7.95 ± 4.46 | 0.274 | 9.36 ± 4.93 | 0.222 | 2.93 ± 2.09 | 0.459 | 6.08 ± 3.01 | 0.216 | 57.7 ± 26.6 | 0.123 |
Abnormal | 32 | 65.3 ± 14.3 | 1.92 ± 1.02 | 5.64 ± 2.80 | 9.00 ± 4.53 | 10.53 ± 4.61 | 2.94 ± 1.53 | 7.00 ± 2.96 | 48.3 ± 23.3 | |||||||||
del(5q)/−5 | (+) | 6 | 68.7 ± 13.3 | 0.393 | 2.18 ± 1.20 | 0.500 | 6.71 ± 3.56 | 0.393 | 10.28 ± 4.58 | 0.233 | 12.33 ± 4.40 | 0.177 | 3.78 ± 2.16 | 0.352 | 8.39 ± 2.36 | 0.048 | 35.4 ± 28.4 | 0.089 |
(−) | 51 | 62.9 ± 14.9 | 1.93 ± 1.52 | 5.35 ± 3.02 | 8.34 ± 4.48 | 9.75 ± 4.76 | 2.84 ± 1.73 | 6.39 ± 3.00 | 54.4 ± 24.1 | |||||||||
del(7q)/−7 | (+) | 8 | 61.5 ± 18.6 | 0.866 | 2.13 ± 1.05 | 0.302 | 6.58 ± 3.00 | 0.111 | 10.44 ± 5.45 | 0.175 | 11.59 ± 4.90 | 0.207 | 3.25 ± 1.51 | 0.261 | 7.06 ± 2.96 | 0.449 | 39.8 ± 24.2 | 0.096 |
(−) | 49 | 63.8 ± 14.2 | 1.93 ± 1.55 | 5.32 ± 3.08 | 8.23 ± 4.30 | 9.76 ± 4.73 | 2.89 ± 1.83 | 6.52 ± 3.02 | 54.5 ± 24.80 | |||||||||
Trisomy 8 | (+) | 8 | 54.4 ± 20.5 | 0.123 | 1.87 ± 1.02 | 0.778 | 6.35 ± 3.84 | 0.628 | 11.09 ± 6.69 | 0.261 | 12.35 ± 6.63 | 0.291 | 2.95 ± 1.64 | 0.813 | 8.29 ± 4.26 | 0.302 | 51.3 ± 27.8 | 0.919 |
(−) | 49 | 65.0 ± 13.2 | 1.97 ± 1.56 | 5.36 ± 2.96 | 8.12 ± 3.97 | 9.64 ± 4.34 | 2.94 ± 1.82 | 6.32 ± 2.69 | 52.6 ± 24.8 | |||||||||
Abn 17p | (+) | 3 | 72.3 ± 10.1 | 0.307 | 2.72 ± 1.47 | 0.324 | 6.05 ± 3.84 | 0.749 | 8.89 ± 5.48 | 0.906 | 10.34 ± 5.00 | 0.880 | 3.72 ± 2.24 | 0.599 | 6.25 ± 1.63 | 0.801 | 45.4 ± 33.9 | 0.623 |
(−) | 54 | 63.0 ± 14.8 | 1.91 ± 1.49 | 5.47 ± 3.07 | 8.52 ± 4.49 | 10.00 ± 4.78 | 2.90 ± 1.77 | 6.62 ± 3.06 | 52.8 ± 24.8 | |||||||||
del(20q) | (+) | 5 | 68.0 ± 10.7 | 0.632 | 2.16 ± 0.55 | 0.186 | 5.56 ± 1.41 | 0.519 | 8.13 ± 2.15 | 0.795 | 9.70 ± 2.27 | 0.712 | 3.13 ± 0.73 | 0.262 | 6.12 ± 1.28 | 0.880 | 44.4 ± 15.0 | 0.327 |
(−) | 52 | 63.1 ± 15.0 | 1.94 ± 1.55 | 5.49 ± 3.20 | 8.58 ± 4.66 | 10.05 ± 4.94 | 2.92 ± 1.85 | 6.65 ± 3.11 | 53.2 ± 25.8 | |||||||||
FISH 1 | (+) | 5 | 54.0 ± 25.2 | 0.428 | 1.61 ± 1.04 | 0.562 | 7.03 ± 4.89 | 0.586 | 11.77 ± 7.84 | 0.368 | 13.19 ± 7.37 | 0.349 | 2.92 ± 2.09 | 0.903 | 8.99 ± 3.72 | 0.128 | 40.4 ± 29.4 | 0.314 |
(−) | 40 | 63.0 ± 13.9 | 1.89 ± 1.18 | 5.49 ± 3.20 | 8.28 ± 3.98 | 9.71 ± 4.24 | 2.86 ± 1.64 | 6.34 ± 2.72 | 51.9 ± 25.4 | |||||||||
FISH 5 | (+) | 8 | 67.3 ± 9.8 | 0.485 | 1.80 ± 1.20 | 0.765 | 5.60 ± 3.63 | 0.921 | 9.17 ± 4.77 | 0.559 | 10.97 ± 4.87 | 0.450 | 2.92 ± 2.23 | 0.579 | 7.86 ± 2.91 | 0.123 | 43.4 ± 30.7 | 0.338 |
(−) | 38 | 61.3 ± 16.2 | 1.85 ± 1.15 | 5.45 ± 2.86 | 8.55 ± 4.52 | 9.88 ± 4.64 | 2.87 ± 1.54 | 6.33 ± 2.87 | 52.1 ± 24.5 | |||||||||
FISH 7 | (+) | 9 | 69.3 ± 7.0 | 0.160 | 1.94 ± 1.08 | 0.605 | 5.57 ± 2.66 | 0.478 | 8.54 ± 3.65 | 0.643 | 10.08 ± 4.10 | 0.723 | 2.92 ± 1.63 | 0.870 | 6.69 ± 2.74 | 0.786 | 44.4 ± 15.04 | 0.461 |
(−) | 37 | 60.6 ± 16.4 | 1.82 ± 1.18 | 5.46 ± 3.06 | 8.68 ± 4.75 | 10.07 ± 4.83 | 2.87 ± 1.67 | 6.58 ± 2.98 | 53.2 ± 25.8 | |||||||||
FISH 8 | (+) | 7 | 59.6 ± 15.5 | 0.490 | 1.90 ± 1.10 | 0.858 | 5.77 ± 3.74 | 1.000 | 9.70 ± 5.85 | 0.697 | 11.43 ± 6.59 | 0.697 | 3.01 ± 1.76 | 0.881 | 7.90 ± 4.44 | 0.549 | 55.6 ± 27.2 | 0.549 |
(−) | 39 | 62.8 ± 15.5 | 1.83 ± 1.17 | 5.43 ± 2.86 | 8.47 ± 4.30 | 9.82 ± 4.29 | 2.85 ± 1.65 | 6.37 ± 2.55 | 49.7 ± 25.5 | |||||||||
FISH 20 | (+) | 4 | 64.3 ± 7.6 | 0.985 | 2.37 ± 1.03 | 0.173 | 5.82 ± 1.49 | 0.417 | 8.38 ± 2.22 | 0.721 | 9.85 ± 2.20 | 0.721 | 3.35 ± 1.06 | 0.229 | 6.02 ± 1.08 | 0.895 | 44.0 ± 15.3 | 0.510 |
(−) | 42 | 62.0 ± 15.8 | 1.78 ± 1.17 | 5.39 ± 3.10 | 8.60 ± 4.74 | 10.00 ± 4.89 | 2.79 ± 1.70 | 6.62 ± 3.06 | 52.0 ± 26.7 |
Survival analysis
Univariable | Multivariable | |||||
---|---|---|---|---|---|---|
Risk factors | HR | 95 % CI |
P
| HR | 95 % CI |
P
|
Revised IPSS | 0.010 | |||||
Very low vs. low | 2.242 | 0.275–18.287 | 0.451 | |||
Very low vs. intermediate | 1.577 | 0.184–13.552 | 0.678 | |||
Very low vs. high | 6.731 | 0.874–51.865 | 0.067 | |||
Very low vs. very high | 6.432 | 0.808–51.197 | 0.079 | |||
Complex CG vs. not | 2.915 | 1.229–6.918 | 0.015 | |||
del(7q)/−7 vs. normal (karyotype) | 4.483 | 1.951–10.302 | <0.001 | |||
FISH 5 abnormal vs. normal | 2.994 | 1.248–7.183 | 0.014 | |||
BM blast ≥10 vs. <10 % | 2.476 | 1.200–5.112 | 0.014 | 2.623 | 1.237–5.563 | 0.012 |
TP53 mutated vs. normal | 4.875 | 2.031–11.703 | <0.001 | 5.257 | 1.341–33.095 | 0.001 |
U2AF1 mutated vs. normal | 2.325 | 1.035–5.222 | 0.041 | 3.544 | 1.485–8.458 | 0.004 |
Percentage of cells with low TL compared to NC ≥80 vs. <80 % | 2.47 | 1.148–5.314 | 0.021 | 2.248 | 1.023 – 4.937 | 0.044 |