PMID- 33549147
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210211
IS  - 2162-3619 (Print)
IS  - 2162-3619 (Electronic)
IS  - 2162-3619 (Linking)
VI  - 10
IP  - 1
DP  - 2021 Feb 6
TI  - Importance of monitoring arsenic methylation metabolism in acute promyelocytic 
      leukemia patients receiving the treatment of arsenic trioxide.
PG  - 10
LID - 10.1186/s40164-021-00205-6 [doi]
LID - 10
AB  - BACKGROUND: Arsenic trioxide [ATO, inorganic arsenite (iAs(III)) in solution] 
      plays an important role in the treatment of acute promyelocytic leukemia (APL). 
      However, the long-term adverse effects (AEs) and the retention of arsenic among 
      APL patients are rarely reported. In this study, we focused on arsenic 
      methylation metabolism and its relationship with chronic hepatic toxicity, as we 
      previously reported, among APL patients who had finished the treatment of ATO. 
      METHODS: A total of 112 de novo APL patients who had completed the ATO-containing 
      treatment were enrolled in the study. Arsenic species [iAs(III), inorganic 
      arsenate (iAs(V)), and their organic metabolites, monomethylarsonic acid (MMA) 
      and dimethylarsinic acid (DMA)] in patients' plasma, urine, hair and nails were 
      detected by high-performance liquid chromatography combined with inductively 
      coupled plasma mass spectrometry (HPLC-ICP-MS). Eighteen single nucleotide 
      polymorphisms (SNPs) of the arsenic (+ 3 oxidative state) methylation transferase 
      (AS3MT) gene, which was known as the main catalyzer for arsenic methylation, were 
      tested with the polymerase chain reaction method. RESULTS: The study showed the 
      metabolic pattern of arsenic in APL patients undergoing and after the treatment 
      of ATO, in terms of total arsenic (TAs) and four species of arsenic. TAs 
      decreased to normal after 6 months since cessation of ATO. But the arsenic 
      speciation demonstrated significantly higher portion of iAs(III) in patient's 
      urine (40.08% vs. 1.94%, P < 0.001), hair (29.25% vs. 13.29%, P = 0.002) and 
      nails (30.21% vs. 13.64%, P = 0.003) than the healthy controls', indicating a 
      decreased capacity of arsenic methylation metabolism after the treatment of ATO. 
      Urine primary methylation index (PMI) was significantly lower in patients with 
      both chronic liver dysfunction (0.14 vs. 0.28, P = 0.047) and hepatic steatosis 
      (0.19 vs. 0.3, P = 0.027), suggesting that insufficient methylation of arsenic 
      might be related to chronic liver disorders. Two SNPs (A9749G and A27215G) of the 
      AS3MT gene were associated with impaired urine secondary methylation index (SMI). 
      CONCLUSIONS: The long-term follow-up of arsenic speciation indicated a decreased 
      arsenic methylation metabolism and a probable relationship with chronic hepatic 
      disorders among APL patients after the cessation of ATO. Urine PMI could be a 
      monitoring index for chronic AEs of ATO, and the SNPs of AS3MT gene should be 
      considered when determining the dosage of ATO.
FAU - Zheng, Yu
AU  - Zheng Y
AD  - Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, 
      National Research Center for Translational Medicine at Shanghai, Ruijin Hospital 
      Affiliated to Shanghai Jiao Tong University School of Medicine, No. 197 Rui Jin 
      Er Road, Shanghai, 200025, China.
FAU - Mao, Yuan-Fei
AU  - Mao YF
AD  - Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, 
      National Research Center for Translational Medicine at Shanghai, Ruijin Hospital 
      Affiliated to Shanghai Jiao Tong University School of Medicine, No. 197 Rui Jin 
      Er Road, Shanghai, 200025, China.
FAU - Zhao, Hui-Jin
AU  - Zhao HJ
AD  - Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, 
      National Research Center for Translational Medicine at Shanghai, Ruijin Hospital 
      Affiliated to Shanghai Jiao Tong University School of Medicine, No. 197 Rui Jin 
      Er Road, Shanghai, 200025, China.
FAU - Chen, Li
AU  - Chen L
AD  - Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, 
      National Research Center for Translational Medicine at Shanghai, Ruijin Hospital 
      Affiliated to Shanghai Jiao Tong University School of Medicine, No. 197 Rui Jin 
      Er Road, Shanghai, 200025, China.
FAU - Wang, Li-Ning
AU  - Wang LN
AD  - Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, 
      National Research Center for Translational Medicine at Shanghai, Ruijin Hospital 
      Affiliated to Shanghai Jiao Tong University School of Medicine, No. 197 Rui Jin 
      Er Road, Shanghai, 200025, China.
FAU - Zhang, Yun-Xiang
AU  - Zhang YX
AD  - Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, 
      National Research Center for Translational Medicine at Shanghai, Ruijin Hospital 
      Affiliated to Shanghai Jiao Tong University School of Medicine, No. 197 Rui Jin 
      Er Road, Shanghai, 200025, China.
FAU - Hu, Jiong
AU  - Hu J
AD  - Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, 
      National Research Center for Translational Medicine at Shanghai, Ruijin Hospital 
      Affiliated to Shanghai Jiao Tong University School of Medicine, No. 197 Rui Jin 
      Er Road, Shanghai, 200025, China.
FAU - Li, Jun-Min
AU  - Li JM
AD  - Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, 
      National Research Center for Translational Medicine at Shanghai, Ruijin Hospital 
      Affiliated to Shanghai Jiao Tong University School of Medicine, No. 197 Rui Jin 
      Er Road, Shanghai, 200025, China. ljm10378@rjh.com.cn.
FAU - Li, Xiao-Yang
AU  - Li XY
AD  - Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, 
      National Research Center for Translational Medicine at Shanghai, Ruijin Hospital 
      Affiliated to Shanghai Jiao Tong University School of Medicine, No. 197 Rui Jin 
      Er Road, Shanghai, 200025, China. lxy11811@rjh.com.cn.
FAU - Zhu, Hong-Ming
AU  - Zhu HM
AD  - Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, 
      National Research Center for Translational Medicine at Shanghai, Ruijin Hospital 
      Affiliated to Shanghai Jiao Tong University School of Medicine, No. 197 Rui Jin 
      Er Road, Shanghai, 200025, China. zhm11931@rjh.com.cn.
LA  - eng
GR  - 81870110/National Natural Science Foundation of China/
GR  - 81770144/National Natural Science Foundation of China/
GR  - 81800141/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20210206
PL  - England
TA  - Exp Hematol Oncol
JT  - Experimental hematology & oncology
JID - 101590676
PMC - PMC7866431
OTO - NOTNLM
OT  - Arsenic methylation metabolism
OT  - Arsenic speciation
OT  - Arsenic trioxide
COIS- The authors declare that they have no competing interests.
EDAT- 2021/02/08 06:00
MHDA- 2021/02/08 06:01
PMCR- 2021/02/06
CRDT- 2021/02/07 20:27
PHST- 2020/12/30 00:00 [received]
PHST- 2021/01/27 00:00 [accepted]
PHST- 2021/02/07 20:27 [entrez]
PHST- 2021/02/08 06:00 [pubmed]
PHST- 2021/02/08 06:01 [medline]
PHST- 2021/02/06 00:00 [pmc-release]
AID - 10.1186/s40164-021-00205-6 [pii]
AID - 205 [pii]
AID - 10.1186/s40164-021-00205-6 [doi]
PST - epublish
SO  - Exp Hematol Oncol. 2021 Feb 6;10(1):10. doi: 10.1186/s40164-021-00205-6.