Background
Materials and methods
Patients
Quantitative real-time PCR
Cytogenetic and gene mutation analysis
Cell culture and knockdown of ACLY
Definition of clinical endpoints and statistical analysis
Results
Patient characteristics
Variable | Low expression | High expression | P value |
---|---|---|---|
Number | 58 | 216 | |
ACLY, median (range) | 0.14 [0.12, 0.16] | 0.33 [0.25, 0.40] | < 0.001 |
Sex, female, n (%) | 38 (65.5) | 134 (62.0) | 0.650 |
Age, median (range), years | 45.50 [31.50, 62.75] | 49.00 [35.00, 60.00] | 0.468 |
WBC, median (IQR), ×109/L | 13.55 [4.03, 34.00] | 25.20 [5.65, 87.00] | 0.010 |
HB, median (IQR), g/L | 87.00 [73.00, 102.00] | 78.80 [65.00, 97.00] | 0.044 |
PLT, median (IQR), ×109/L | 42.50 [22.00, 70.75] | 42.00 [21.00, 77.00] | 0.980 |
BM blast, median (IQR), % | 65.75 [49.62, 81.25] | 70.14 [52.34, 84.25] | 0.541 |
FAB classification, n (%) | 0.166 | ||
M0 | 3 (5.2) | 21 (9.7) | |
M1 | 7 (12.1) | 20 (9.3) | |
M2 | 29 (50.0) | 86 (39.8) | |
M4 | 6 (10.3) | 20 (9.3) | |
M5 | 11 (19.0) | 62 (28.7) | |
M6 | 2 (3.4) | 1 (0.5) | |
AML | 0 (0.0) | 6 (2.8) | |
Cytogenetic risks, n (%) | 0.110 | ||
Favorable | 9 (15.5) | 15 (6.9) | |
Intermediate | 42 (72.4) | 177 (81.9) | |
Poor | 7 (12.1) | 24 (11.1) | |
Gene mutations, n (%) | |||
FLT3-ITD | 6 (11.5) | 30 (14.6) | 0.660 |
CEBPADM | 10 (20.0) | 10 (5.0) | 0.002 |
NPM1 | 12 (22.2) | 56 (26.7) | 0.602 |
DNMT3A | 1 (1.8) | 23 (10.8) | 0.035 |
Treatment, n (%)a | 0.982 | ||
DA | 22 (37.9) | 78 (36.1) | |
HAA | 17 (29.3) | 63 (29.2) | |
IA | 19 (32.8) | 75 (34.7) |
Prognostic significance of ACLY expression in Chinese AML patients
Variables | Univariate analysis | Multivariate analysis | ||
---|---|---|---|---|
P value | HR (95% CI) | P value | HR (95% CI) | |
ACLY expression (high vs. low) | 0.001 | 2.19 (1.38, 3.475) | 0.029 | 1.805 (1.062, 3.068) |
Age | < 0.001 | 1.007 (1.004, 1.011) | 0.009 | 1.006 (1.001, 1.01) |
WBC | < 0.001 | 1.005 (1.003, 1.007) | < 0.001 | 1.004 (1.002, 1.006) |
Cytogenetic risks | ||||
Intermediate vs. favorable | 0.003 | 3.811 (1.556, 9.337) | 0.027 | 3.748 (1.164, 12.069) |
Poor vs. favorable | < 0.001 | 8.539 (3.247, 22.454) | 0.001 | 7.978 (2.34, 27.197) |
Gene mutations (mutation vs. wild-type) | ||||
FLT3-ITD | 0.022 | 1.66(1.076, 2.56) | 0.007 | 1.969(1.208,3.21) |
NPM1 | 0.051 | 1.434(0.998,2.061) | 0.812 | 1.05(0.702,1.571) |
CEBPADM | 0.022 | 0.385(0.169,0.874) | 0.040 | 0.409(0.175,0.960) |
DNMT3A | 0.001 | 2.474(1.483,4.125) | 0.022 | 1.98(1.105,3.546) |
Treatmenta | ||||
HAA vs. DA | 0.001 | 0.503 (0.335, 0.756) | 0.007 | 0.536 (0.341, 0.842) |
IA vs. DA | 0.003 | 0.567 (0.391, 0.824) | 0.002 | 0.48 (0.304, 0.756) |