Characteristics of myeloid sarcoma in mice and patients with TET2 deficiency

Jinhuan Wang, Zhaoyi Miao, Yanan Jiang, Ping Zou, Weiming Li, Xiaoqiong Tang, Yangyang Lv, Donghui Xing, Shi Chen, Fengchun Yang, Mingjiang Xu, Zeng Cao, Haitao Wang, Zhigang Zhao

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3789-3798
Number of pages10
JournalOncology Letters
Volume19
Issue number6
DOIs
StatePublished - Jun 1 2020
Externally publishedYes

Keywords

  • Acute myeloid leukemia
  • Myelodysplastic syndrome
  • Myeloid Sarcoma
  • Ten-eleven translocation-2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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