Clinical characteristics and prognostic study of adult acute myeloid leukemia patients with ASXL1 mutations

Figures & data

Table 1. Characteristics of AML patients with and without ASXL1 mutations.

Parameter	ASXL1 mutation Negative (n = 134)	ASXL1 mutation Positive (n = 22)	P-value
Male/female	69/65	12/10	0.791
Age (years)	47 (14–85)	49 (20–75)	0.605
WBC (*10^9/L)	34.39 (0.58–431.4)	53.06 (0.74–322.71)	0.274
Hb (g/l)	75 (41–143)	76 (46–115)	0.721
PLT (*10^9)	61 (3–496)	50 (7–215)	0.533
Peripheral blood blasts (%)	42 (0–97)	46 (0–98)	0.661
Bone marrow blasts (%)	60.0 (58.0–98.0)	60.5 (8.0–90.0)	0.978
LDH (IU/L)	657 (129–6160)	466 (125–1437)	0.416
α-HBDH ((IU/L))	565 (111–4165)	401 (114–1302)	0.476
UA (Uric Acid) (mmol/l)	333 (84–896)	386 (105–2121)	0.643

Table 2. AML patients with and without ASXL1 mutations and FAB classification.

FAB (149)	ASXL1 mutations (n = 127)	ASXL1 mutations wild type (n = 22)	P = 0.416*
M0 Non-M0	1 (50%) 126 (85.71%)	1 (50%) 21 (14.68%)	P = 0.274
M1 Non-M1	5 (83.33%) 122 (85.31%)	1 (16.67%) 21 (14.68%)	p ≈ 1.000
M2 Non-M2	41 (93.18%) 86 (81.90%)	3 (6.82%) 19 (18.10%)	P = 0.077
M4 Non-M4	1 (100%) 126 (85.14%)	0 (0%) 22 (15.38%)	p ≈ 1.000
M5 Non-M5	71 (82.56%) 56 (88.89%)	15 (17.44%) 7 (11.11%)	P = 0.282
M6 Non-M6	9 (90%) 118 (84.89%)	1 (10.00%) 21 (15.11%)	p ≈ 1.000

Table 3. AML patients with and without ASXL1 mutations and chromosome karyotype.

	ASXL1 mutation Negative (n = 134)	ASXL1 mutation Positive (n = 22)
Karyotype categories			P = 0.590^a
Good	9 (81.82%)	2 (18.18%)
Intermediate	78 (85.71%)	13 (14.29%)
Poor	10 (100%)	0 (%)
Unknown	37 (84.09%)	7 (15.91%)
CN-AML	49 (85.96%)	8 (14.04%)	P = 0.642^b
Non-CN-AML	33 (82.5%)	7 (17.5%)

Table 4. ASXL1 mutations and some other common AML prognosis-related mutations.

Gene mutations	ASXL1 mutation Negative (n = 134)	ASXL1 mutation Positive (n = 22)
IDH1
Positive	2 (50%)	2 (50%)	P = 0.096
Negative	132 (86.84%)	20 (13.16%)
IDH2
Positive	10 (71.43%)	4 (28.57%)	P = 0.114
Negative	124 (87.32%)	18 (12.68%)
NPM1
Positive	10 (90.91%)	1 (9.09%)	P = 0.963
Negative	121 (85.21%)	21 (14.79%)
TENegativeT2
Positive	16 (57.14%)	12 (42.86%)	P < 0.001
Negative	118 (92.19%)	10 (7.81%)
DNMT3A
Positive	17 (62.96%)	10 (37.04%)	P = 0.001
Negative	117 (90.70%)	12 (9.3%)
CEBPA
Positive	18 (81.82%)	4 (18.18%)	P = 0.793
Negative	116 (86.57%)	18 (13.43%)
FLT3-ITD
Positive	19 (100%)	0 (0%)	P = 0.125
Negative	115 (83.94%)	22 (16.06%)
C-kit^D816
Positive	5 (100%)	0(0%)	P ≈ 1.000
Negative	129 (85.43%)	22(16.06%)
PHF6
Positive	3 (50%)	3 (50%)	P = 0.037
Negative	131 (87.33%)	19 (12.67%)
Dup-MLL
Positive	4 (57.14%)	3 (42.86%)	P = 0.059
Negative	130 (97.25%)	19 (12.75%)

Figure 1. The K-M survival curve of ASXL1 mutations in total AML patients. (a) OS (n = 145), (b) EFS (n = 139).

Table 5. Survival analysis (OS and DFS) in 55 CN-AML patients.

Factors		OS		DFS
		P-value	RR	P-value	RR
Gentle (patients)
Man	30	0.528	1.035	0.704	1.139
Woman	25
Age (years)
≥60	14	<0.0001	4.403	0.007	2.739
<60	41
WBC (*10^9/L)^a
Median	10.5	0.931	1.035	0.362	1.370
Range	0.74–163.2
Hb (g/l)
≥60	43	0.465	0.722	0.538	0.786
<60	12
PLT (*10^9/L)
≥30	36	0.347	0.681	0.684	0.865
<30	19
Peripheral blood blasts (%)^a
Median	21	0.829	1.091	0.888	1.050
Range	0–98
Bone marrow blasts (%)^a
Median	61.5	0.932	1.035	0.516	1.254
Range	5.5–95.5
α-HBDH (IU/L)^a
Median	271	0.045	2.320	0.127	1.710
Range	111–1897
UA (mmol/L)^a
Median	319	0.254	1.587	0.108	1.752
Range	116–896
ASXL1, no (%)
Mutated	8	0.022	3.229	0.173	1.955
Wild-type	47
TET2, no (%)
Mutated	9	0.411	1.511	0.213	1.708
Wild-type	46
CEBPA, no (%)
Mutated	6	0.296	0.462	0.447	0.665
Wild-type	49
NPM1, no (%)
Mutated	1	0.558	0.047	0.471	2.093
Wild-type	54
Dnmt3a, no (%)
Mutated	8	0.170	1.908	0.290	1.573
Wild-type	47
FLT3-ITD, no (%)
Mutated	5	0.961	0.964	0.704	1.139
Wild-type	50

Table 6. Multivariate analysis of CN-AML patients on long-term survival.

Factors	OS			DFS
	HR	95% CI	P	HR	95% CI	P
ASXL1	3.070	1.095–8.604	0.033	1.754	0.657–4.687	0.262
Age(years)	2.338	2.338–12.447	<0.001	3.087	1.454–6.554	0.003
α-HBDH(IU/L)	1.062	1.062–5.745	0.036	1.798	0.889–3.638	0.103

Figure 2. The K-M survival curve of ASXL1 mutations in CN-AML patients, (a) OS (n = 55), (b) DFS (n = 55).

Figure 3. The K-M survival curve of ASXL1 mutations in AML (age > 0 years) patients, (a) OS (n = 36), (b) DFS (n = 33)

Table 7. Influencing factors analysis on survival (OS and DFS) of 36 elderly (≥60 years) AML patients.

Factors		OS		DFS
		P-value	RR	P-value	RR
Gentle (patients)
Man	23	0.414	0.715	0.992	1.004
Woman	13
Karyotype
Good	1	0.348	1.263	0.383	0.811
Intermediate	14
Poor	9
Unknown	12
WBC (*10^9/L)*
Median	13.08	0.175	1.711	0.307	1.488
Range	0.74–136.4
Hb (g/l)
≥60	27	0.866	0.928	0.500	0.787
<60	9
PLT (*10^9/L)
≥30	24	0.100	0.522	0.624	0.824
<30	12
Peripheral blood blasts (%)*
Median	32	0.52	1.279	0.462	1.328
Range	0–98	5
Bone marrow blasts (%)*
Median	69.5	0.96	1.019	0.110	1.879
Range	5.5–95.5	1
α-HBDH(IU/L)*
Median	364	0.02	2.479	0.004	3.477
Range	111–4165	5
UA*
Median	357	0.89	0.949	0.792	0.900
Range	84–896	2
ASXL1
Mutated	4	0.01	3.991	0.108	2.472
Wild-type	32	9
TET2
Mutated	5	0.86	1.095	0.915	1.060
Wild-type	31	8
CEBPA
Mutated	3	0.23	0.196	0.124	0.208
Wild-type	33	4
NPM1
Mutated	4	0.59	0.625	0.940	1.047
Wild-type	32	5
DNMT3A
Mutated	7	0.36	1.582	0.875	1.082
Wild-type	29	4
FLT3-ITD
Mutated	6	0.20	1.914	0.194	1.921
Wild-type	30	0

Table 8. Multivariate analysis of elderly (≥60 years) AML patients on long-term survival.

Factors	OS			DFS
	HR	95% CI	P	HR	95% CI	P
ASXL1	10.435	2.594–41.977	0.001	6.336	2.206–18.196	0.003
α-HBDH(IU/L)	4.120	1.587–10.694	0.004	8.717	2.120–35.845	0.003

Figure 4. The K-M survival curve of TET2 mutations in total AML patients, (a) OS (n = 145), (b) DFS (n = 139); The K-M survival curve of TET2 mutations when accompanied with ASXL1 mutations in AML patients, (c) OS (n = 25), (d) DFS (n = 25).

Figure 5. The K-M survival curve of DNMT3A mutations in total AML patients, (a) OS (n = 145), (b) DFS (n= 139); The K-M survival curve of DNMT3A mutations when accompanied with ASXL1 mutations in AML patients, (c) OS (n = 24), (d) DFS (n = 24).

Figure 6. The K-M survival curve of CEBPA mutations in total AML patients, (a) OS (n = 145), (b) DFS (n = 139); The K-M survival curve of CEBPA mutations when accompanied with ASXL1 mutations in AML patients, (c) OS (n = 21), (d) DFS (n = 21).