Genetic mutations associated with blood count abnormalities in myeloid neoplasms

Figures & data

Figure 1. Genetic abnormalities in myelodysplastic syndrome (MDS) and myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) in the study. (A) Cytogenetic study in low-risk MDS, high-risk MDS and MDS/MPN. (B) Frequency of somatic mutations in low-risk MDS, high-risk MDS and MDS/MPN. (C) Mutation landscape of patients with MDS and MDS/MPN.

Table 1. Baseline characteristics of patients.

	Total (N = 168)	Low risk (N = 92)	High risk (N = 57)	MDS/MPN (N = 19)	P-value
Age (years), median (IQR)	71 (63–78)	72 (63.5–81)	70 (63–78)	72 (62–75)	0.28
Female, n (%)	86 (51.2)	43 (46.7)	32 (56.1)	11 (57.9)	0.44
WBC [x10^9/L, median (IQR)]	4.12 (2.56–6.85)	4.123 (2.98–6.24)	2.96 (1.96–5.50)	26.92 (10.71–197.33)	<0.001
ANC < 0.5 × 10^9/L, n (%)	12 (7.2)	2 (2.2)	10 (17.5)	0 (0)	0.002
Platelet cell [x10^9/L, median (IQR)]	100 (58–204)	115.5 (62.5–240)	87 (43.5–123)	159 (51–220)	0.03
Haemoglobin [g/dL, median (IQR)]	8.3 (7–10)	8.6 (7.4–10.5)	8.1 (6.9–9)	8.1 (5.5–10.6)	0.05
Normal Karyotype, n (%)	102 (60.7)	65 (70.7)	27 (47.4)	10 (52.6)	0.02
Number of mutations per patient, median (IQR)	1 (0–3)	1 (0–2)	2 (1–3)	3 (1–4)	<0.001
Patients with mutations, n (%)	121 (72)	52 (56.5)	51 (89.5)	18 (94.7)	<0.001

Notes: Differences in continuous and categorical variables between three groups were assessed using a Kruskall Wallis test and Chi-square test or fisher exact test, respectively.

Table 2. Association between SF3B1 and U2AF1 mutational status with haemoglobin, platelet, and white blood cell count levels.

	No SF3B1 mutation (N = 151)	SF3B1 mutation (N = 16)	P-value
Haemoglobin (g/dL)	8.4 (7.1–10.1)	7.9 (6.8–8.9)	0.02
Platelet (×10^9/L)	93 (56–184)	286 (160.5–449.5)	<0.001
	No U2AF1 mutation (N = 153)	U2AF1 mutation (N = 14)	P-value
White blood cell (×10^9/L)	4.18 (2.61–7.23)	3.05 (1.89–4.12)	0.02

Figure 2. Factors associated with overall survival rates. (A) Survival rates in low-risk MDS, high-risk MDS and MDS/MPN. (B) Survival rates of patients with normal, abnormal, and complex karyotypes. (C) Survival rates of patients with increasing numbers of mutations.

Figure 3. Association of somatic mutations and overall survival rates using univariate analysis. (A) ASXL1, (B) RUNX1, (C) SRSF2, (D) TP53, (E) SETBP1, (F) STAG2.

Table 3. Risk factors associated with mortality rates.

	Univariate		Multivariate
	HR (95%CI)	P-value	aHR (95%CI)	P-value
Risk group
Low-risk MDS	1		1
High-risk MDS	3.98 (2.46–6.44)	<0.001	3.45 (2.11–5.65)	<0.001
MDS/MPN	2.92 (1.48–5.75)	<0.001	2.64 (1.33–5.26)	0.01
ANC < 0.5 × 10^9/L	3.9 (2.11–7.23)	<0.001	4.03 (2.16–7.53)	<0.001
ANC < 1 × 10^9/L	2.05 (1.28–3.29)	<0.001
Platelet < 50 × 10^9/L	1.31 (0.79–2.18)	0.29
Platelet < 100 × 10^9/L	1.29 (0.83–1.99)	0.25
Haemoglobin < 7 g/dL	1.32 (0.82–2.11)	0.25
Mutation group
No mutation	1
1	1.68 (0.82–3.44)	0.15
2	2.6 (1.24–5.47)	0.01
3	3.16 (1.46–6.84)	<0.001
≥4	5.54 (2.7–11.37)	<0.001
ASXL1	2.46 (1.49–4.07)	<0.001	1.75 (1.03–2.99)	0.04
RUNX1	2.76 (1.49–5.11)	<0.001
SRSF2	2.2 (1.25–3.86)	0.01
TP53	2.3 (1.22–4.35)	0.01
SETBP1	2.84 (1.41–5.7)	<0.001	2.33 (1.11–4.87)	0.03
STAG2	2.49 (1.2–5.19)	0.02

Notes: HR: Hazard ratio, aHR: adjusted Hazard ratio. The Cox regression was used to determine the factors associated mortality rate. Multivariate models were developed by adjusting for covariates with p < 0.1 in univariate models and stepwise back ward LR to select the final model.