The Evaluation of iron overload through hepcidin level and its related factors in myelodysplastic syndromes

Figures & data

Figure 1. Bone marrow hepcidin levels vs. peripheral blood hepcidin levels in MDS patients. There was no significant difference between bone marrow hepcidin levels and peripheral blood hepcidin levels in MDS patients (P = 0.134).

Table 1. Characteristics of MDS patients and controls

	MDS (n = 73)	Controls (n = 28)
Age (years)	19–87 (62)	17–70 (39)
Gender (male/female)	39/34	18/10
Disease category, no. (%)*
RCUD	11 (15)	–
RARS	7 (9)	–
RCMD	21 (29)	–
RAEB-1	11 (15)	–
RAEB-2	10 (14)	–
MDS-U	8 (11)	–
5q^− syndrome	5 (7)	–
Cytogenetic risk group, no. (%)^†
Good	51 (70)	28 (100)^‡
Intermediate	17 (23)	–
Poor	5 (7)	–
BM hepcidin (ng/ml)	265.66 ± 102.77	335.71 ± 25.16
PB hepcidin (ng/ml)	301.61 ± 91.56	–
Ferritin (μg/l)	621 (59–7855)	66 (59–77)
CRP (mg/l)	7.19 (2.23–173.00)	4.01 (2.45–11.70)
EPO (mIU/ml)	293 (11–11883)	15 (8–30)
GDF15 (2^−ΔΔCt)	2.27 (0.06–27.67)	1.10 (0.06–7.36)
TWSG1 (2^−ΔΔCt)	2.04 (0.01–17.88)	1.06 (0.06–3.81)
Cardiac T2* (ms)^§	25.78 ± 1.82	–
LIC (mg/g dry weight)^§	17.66 ± 1.87	–

*Patients with MDS were classified according to the WHO2008 classification.

^†Classified by IPSS criteria.

^‡All the controls had normal karyotype.

^§Only 24 MDS patients underwent the MRI T2* test, including 4 RCUD, 2 RARS, 11 RCMD, 3 RAEB-1, and 4 MDS-U patients.

Table 2. Characteristics of MDS patients stratified according to WHO subtypes

	RCUD (n = 11)	RARS (n = 7)	RCMD (n = 21)	RAEB-1 (n = 11)	RAEB-2 (n = 10)	MDS-U (n = 8)	5q- syndrome (n = 5)	P
Age (years)	69 (19–84)	62 (51–80)	42 (20–87)	66 (43–79)	65 (44–72)	28 (19–84)	54 (46–81)	0.008
Gender (male %)	54.5	42.9	66.7	45.5	40	50	60	0.818
Hepcidin (ng/ml)	265.66 ± 46.77	105.40 ± 5.13	237.16 ± 93.81	335.71 ± 25.16	301.09 ± 30.58	306.08 ± 44.24	299.49 ± 10.66	0.041
Ferritin (μg/l)	66 (59–77)	921 (805–1355)	1444 (215–4915)	985 (124–7855)	629 (169–2688)	78 (62–92)	598 (267–1440)	0.001
Hepcidin/ferritin	4.19 (3.89–5.15)	0.12 (0.09–0.15)	0.21 (0.04–1.26)	1.58 (0.03–2.23)	1.14 (0.19–1.56)	3.37 (2.89–5.41)	0.67 (0.33–1.01)	0.001
CRP (mg/l)	4.16 (2.70–10.80)	7.30 (4.58–15.70)	3.03 (2.23–35.00)	20.70 (4.27–173.00)	6.57 (3.60–11.10)	5.57 (3.75–12.19)	3.66 (2.20–6.88)	0.004
EPO (mIU/ml)	40 (28–79)	399 (26–787)	947 (18–11883)	695 (25–990)	498 (30–650)	20 (11–27)	78 (26–205)	0.001
GDF15 (2^−ΔΔCt)	4.34 (0.06–11.27)	12.76 (3.03–27.67)	4.11 (0.43–13.38)	0.62 (0.51–0.84)	5.67 (1.09–12.88)	2.41 (1.84–8.22)	3.96 (0.95–5.36)	0.006
TWSG1 (2^−ΔΔCt)	1.96 (1.39–2.50)	7.41 (0.33–17.88)	2.36 (2.33–15.35)	1.04 (0.60–1.73)	1.84 (0.58–2.78)	0.92 (0.01–3.27)	1.17 (0.24–4.89)	0.321
Cardiac T2* (ms)*	17.75 ± 5.05	22.20 ± 8.10	16.50 ± 2.30	25.00 ± 1.70	–	31.05 ± 1.05	–	0.574
LIC (mg/g dry weight)*	21.22 ± 3.66	22.41 ± 1.32	30.71 ± 0.45	21.25 ± 6.86	–	14.24 ± 12.97	–	0.071

*Only twenty-four MDS patients underwent the MRI T2* test, including 4 RCUD, 2 RARS, 11 RCMD, 3 RAEB-1, and 4 MDS-U patients.

Table 3. Characteristics of MDS patients stratified according to IPSS and WPSS

	IPSS			WPSS
	Low risk (n = 46)	High risk (n = 27)	P	Low risk (n = 42)	High risk (n = 31)	P
Hepcidin (ng/ml)	278.31 ± 21.91	222.99 ± 26.78	0.033	299.91 ± 16.83	223.76 ± 23.92	0.009
Ferritin (μg/l)	886 (59–2868)	832 (206–7855)	0.689	459 (66–1399)	2590 (676–7855)	0.028
CRP (mg/l)	3.03 (2.23–35.00)	7.90 (4.18–173.00)	0.068	3.03 (2.23–35.00)	8.20 (3.84–173.00)	0.028
EPO (mIU/ml)	419 (11–11883)	694 (78–1807)	0.853	317 (11–11883)	802 (26–1460)	0.059
GDF15 (2^−ΔΔCt)	3.09 (0.34–27.67)	2.83 (0.06–17.39)	0.281	3.88 (0.06–17.39)	5.56 (0.34–27.67)	0.048
TWSG1 (2^−ΔΔCt)	2.27 (0.60–15.35)	1.72 (0.01–17.88)	0.920	2.07 (0.01–15.14)	2.20 (0.03–17.88)	0.786

Table 4. Transfusion-dependent patients vs. transfusion-independent patients

	Transfusion-dependent (n = 33)	Transfusion-independent (n = 40)	P
Hepcidin(ng/ml)	225.37 ± 19.02	323.68 ± 18.80	0.001
Ferritin (μg/l)	1293 (123–7855)	227 (66–880)	0.004
CRP (mg/l)	7.30(2.23–173.00)	5.19 (3.24–10.20)	0.223
EPO (mIU/ml)	1050 (11–11883)	29 (16–79)	0.007
GDF15 (2^−ΔΔCt)	6.37 (0.06–27.67)	1.38 (0.34–14.76)	<0.001
TWSG1 (2^−ΔΔCt)	2.64 (0.02–17.88)	0.20 (0.01–1.00)	<0.001
Cardiac T2* (ms)*	19.85 ± 2.22	26.97 ± 2.05	0.148
LIC (mg/g dryweight)*	20.52 ± 1.57	3.37 ± 1.18	<0.001

*Among the 24 patients who have undergone MRI T2* test, 19 of them were transfusion-dependent, the other five were transfusion-independent.

Figure 2. The expression levels of hepcidin in CD4⁺ lymphocytes and CD19⁺ lymphocytes in non-transfusion-treated MDS patients. The expression level of hepcidin in CD4⁺ high-expression group is higher than the normal-expression group. Statistical difference has been found (P = 0.02). There is no significant difference between CD19⁺ high-expression group and normal-expression group (P = 0.206).

Figure 3. Hepcidin levels in T-cell polarization of Th1/Th2 in non-transfusion-treated MDS patients. There is a significant difference between Th1/Th2 > 70.6 group and Th1/Th2 ≦ 70.6 group (P < 0.001). If the ratio of Th1/Th2 is over 70.6, it is considered that the patient has a Th1 polarization trend.

Figure 4. The MRI T2* images of one MDS patient whose SF < 1000 µg/l. The MRI T2* images of one MDS patient whoseSF < 1000 µg/l. The patient's SF value is 897 µg/l, but his LIC is 17.56 mg/g dry weight which means severe iron overload.

Table 5. Linear regression model of hepcidin predictors in MDS patients

	r	P
Age (years)	0.588	0.064
Ferritin (μg/l)	0.508	0.095
CRP (mg/l)	0.302	0.001
EPO (mIU/ml)	0.543	0.072
GDF15 (2^−ΔΔCt)	−0.019	0.897
TWSG1 (2^−ΔΔCt)	−0.170	0.411
Cardiac T2* (ms)	0.433	0.825
LIC (mg/g dry weight)	0.298	0.031