TY - JOUR
T1 - Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis
AU - Kinjo, Tadamune
AU - Inoue, Hirosuke
AU - Kusuda, Takeshi
AU - Fujiyoshi, Junko
AU - Ochiai, Masayuki
AU - Takahata, Yasushi
AU - Honjo, Satoshi
AU - Koga, Y.
AU - Hara, Toshiro
AU - Ohga, Shouichi
N1 - Funding Information:
The authors declare no conflicts of interests in association with this study. This study was supported in part by the Japan Society for the Promotion of Science KAKENHI: #15K09717, #16K19688 and #17K16300. We thank Dr. Hiroaki Kurata and Dr. Masako Ichiyama (Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University) for their involvement in the management of the TAM patients, and Dr. Kazuaki Yasuoka and Ms. Tamami Tanaka (Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University) for the measurement of the serum cytokine/chemokine concentrations.
Funding Information:
The authors declare no conflicts of interests in association with this study. This study was supported in part by the Japan Society for the Promotion of Science KAKENHI : # 15K09717 , # 16K19688 and # 17K16300 .
Publisher Copyright:
© 2018
PY - 2019/8
Y1 - 2019/8
N2 - Background: Transient abnormal myelopoiesis (TAM) is a neonatal preleukemic syndrome that occurs exclusively in neonates with Down syndrome (DS). Most affected infants spontaneously resolve, although some patients culminate in hepatic failure despite the hematological remission. It is impossible to determine the patients who are at high risk of progressive liver disease and leukemic transformation. The objective is to search for biomarkers predicting the development of hepatic failure in DS infants with TAM. Methods: Among 60 newborn infants with DS consecutively admitted to our institutions from 2003 to 2016, 41 infants with or without TAM were enrolled for the study. Twenty-two TAM-patients were classified into “progression group” (n = 7) that required any therapy and “spontaneous resolution group” (n = 15). Serum concentrations of chemokines (CXCL8, CXCL9, CXCL10, CCL2 and CCL5) and transforming growth factor (TGF)-β1 were measured at diagnosis of TAM for assessing the outcome of progressive disease. Results: Three patients developed leukemia during the study period (median, 1147 days; range, 33–3753). Three died of hepatic failure. All patients in the progression group were preterm birth <37 weeks of gestational age and were earlier than those in the spontaneous resolution group (median, 34.7 vs. 37.0 weeks, p < 0.01). The leukocyte counts and CXCL8 and CCL2 levels at diagnosis in the progression group were higher than those in the spontaneous resolution group (leukocyte: median, 81.60 vs. 27.30 × 109/L, p = 0.01; CXCL8: 173.8 vs. 34.3 pg/ml, p < 0.01; CCL2: 790.3 vs. 209.8 pg/mL, p < 0.01). Multivariate analyses indicated that an increased CCL2 value was independently associated with the progression and CXCL8 with the death of liver failure, respectively (CCL2: standardized coefficient [sc], 0.43, p < 0.01; CXCL8: sc = −0.46, p = 0.02). Conclusion: High levels of circulating CXCL8 and CCL2 at diagnosis of TAM may predict progressive hepatic failure in DS infants.
AB - Background: Transient abnormal myelopoiesis (TAM) is a neonatal preleukemic syndrome that occurs exclusively in neonates with Down syndrome (DS). Most affected infants spontaneously resolve, although some patients culminate in hepatic failure despite the hematological remission. It is impossible to determine the patients who are at high risk of progressive liver disease and leukemic transformation. The objective is to search for biomarkers predicting the development of hepatic failure in DS infants with TAM. Methods: Among 60 newborn infants with DS consecutively admitted to our institutions from 2003 to 2016, 41 infants with or without TAM were enrolled for the study. Twenty-two TAM-patients were classified into “progression group” (n = 7) that required any therapy and “spontaneous resolution group” (n = 15). Serum concentrations of chemokines (CXCL8, CXCL9, CXCL10, CCL2 and CCL5) and transforming growth factor (TGF)-β1 were measured at diagnosis of TAM for assessing the outcome of progressive disease. Results: Three patients developed leukemia during the study period (median, 1147 days; range, 33–3753). Three died of hepatic failure. All patients in the progression group were preterm birth <37 weeks of gestational age and were earlier than those in the spontaneous resolution group (median, 34.7 vs. 37.0 weeks, p < 0.01). The leukocyte counts and CXCL8 and CCL2 levels at diagnosis in the progression group were higher than those in the spontaneous resolution group (leukocyte: median, 81.60 vs. 27.30 × 109/L, p = 0.01; CXCL8: 173.8 vs. 34.3 pg/ml, p < 0.01; CCL2: 790.3 vs. 209.8 pg/mL, p < 0.01). Multivariate analyses indicated that an increased CCL2 value was independently associated with the progression and CXCL8 with the death of liver failure, respectively (CCL2: standardized coefficient [sc], 0.43, p < 0.01; CXCL8: sc = −0.46, p = 0.02). Conclusion: High levels of circulating CXCL8 and CCL2 at diagnosis of TAM may predict progressive hepatic failure in DS infants.
UR - http://www.scopus.com/inward/record.url?scp=85054429688&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054429688&partnerID=8YFLogxK
U2 - 10.1016/j.pedneo.2018.09.005
DO - 10.1016/j.pedneo.2018.09.005
M3 - Article
C2 - 30314728
AN - SCOPUS:85054429688
SN - 1875-9572
VL - 60
SP - 382
EP - 388
JO - Acta Paediatrica Sinica
JF - Acta Paediatrica Sinica
IS - 4
ER -