TY - JOUR
T1 - Characteristics of myeloid sarcoma in mice and patients with TET2 deficiency
AU - Wang, Jinhuan
AU - Miao, Zhaoyi
AU - Jiang, Yanan
AU - Zou, Ping
AU - Li, Weiming
AU - Tang, Xiaoqiong
AU - Lv, Yangyang
AU - Xing, Donghui
AU - Chen, Shi
AU - Yang, Fengchun
AU - Xu, Mingjiang
AU - Cao, Zeng
AU - Wang, Haitao
AU - Zhao, Zhigang
N1 - Funding Information:
This research was funded by the National Natural Science Foundation of China (grant no. 81870150), the National Natural Science Foundation of China (grant no. 81670102) the Natural Science Foundation of Tianjin (grant no. 16JCYBJC25200) and the National Natural Science Foundation of China (grant no. 81572543).
Publisher Copyright:
© 2020 Spandidos Publications. All rights reserved.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Myeloid sarcoma (MS) carries a poor prognosis, and information on epigenetic modifications in MS is currently limited. In the present study, 214 ten-eleven translocation-2 (TET2)-/- mice were successfully constructed. In addition, 436 patients with myelodysplastic syndrome (MDS) and 354 with acute myeloid leukemia (AML) patients were recruited. The incidence of MS in mice and patients with TET2 deficiency was examined, and the efficiency of hypomethylating agents (HMAs) was also be evaluated. A total of 93% of the TET2-/- mice developed myeloid malignancies, 5.5% of which were accompanied by MS (n=11). The survival of these TET2-/- mice ranged between 3 and 25 months. No significant difference was observed between the survival of MS and non-MS mice with TET2 loss (P>0.05). In addition, MS cells were transplantable, and their recipients exhibited myeloproliferative characteristics, such as increased white blood cell counts, monocytosis, low erythrocyte counts and hepatosplenomegaly. Their median survival duration was 94.8 days. In the clinical setting, 9.7% of MDS and 11.6% of AML patients with TET2 deficiency developed MS, which was higher compared with previous reports (1.5-9.1%). The median age of the MS patients was 44 years old. 5-Aza-2'-deoxycytidine (5-Aza-dC) reduced the incidence of MS in TET2-/- mice, and decitabine was a suitable treatment strategy for MS patients. These data indicate that TET2 deficiency plays a key role in MS and its prognostic significance requires further investigation. HMAs may be a useful treatment for MS patients with TET2 mutations.
AB - Myeloid sarcoma (MS) carries a poor prognosis, and information on epigenetic modifications in MS is currently limited. In the present study, 214 ten-eleven translocation-2 (TET2)-/- mice were successfully constructed. In addition, 436 patients with myelodysplastic syndrome (MDS) and 354 with acute myeloid leukemia (AML) patients were recruited. The incidence of MS in mice and patients with TET2 deficiency was examined, and the efficiency of hypomethylating agents (HMAs) was also be evaluated. A total of 93% of the TET2-/- mice developed myeloid malignancies, 5.5% of which were accompanied by MS (n=11). The survival of these TET2-/- mice ranged between 3 and 25 months. No significant difference was observed between the survival of MS and non-MS mice with TET2 loss (P>0.05). In addition, MS cells were transplantable, and their recipients exhibited myeloproliferative characteristics, such as increased white blood cell counts, monocytosis, low erythrocyte counts and hepatosplenomegaly. Their median survival duration was 94.8 days. In the clinical setting, 9.7% of MDS and 11.6% of AML patients with TET2 deficiency developed MS, which was higher compared with previous reports (1.5-9.1%). The median age of the MS patients was 44 years old. 5-Aza-2'-deoxycytidine (5-Aza-dC) reduced the incidence of MS in TET2-/- mice, and decitabine was a suitable treatment strategy for MS patients. These data indicate that TET2 deficiency plays a key role in MS and its prognostic significance requires further investigation. HMAs may be a useful treatment for MS patients with TET2 mutations.
KW - Acute myeloid leukemia
KW - Myelodysplastic syndrome
KW - Myeloid Sarcoma
KW - Ten-eleven translocation-2
UR - http://www.scopus.com/inward/record.url?scp=85083671585&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85083671585&partnerID=8YFLogxK
U2 - 10.3892/ol.2020.11479
DO - 10.3892/ol.2020.11479
M3 - Article
C2 - 32382331
AN - SCOPUS:85083671585
SN - 1792-1074
VL - 19
SP - 3789
EP - 3798
JO - Oncology Letters
JF - Oncology Letters
IS - 6
ER -