Antibiotic treatment ameliorates Ten-eleven translocation 2 (TET2) loss-of-function associated hematological malignancies. Academic Article uri icon

abstract

  • TET2 is among the most frequently mutated genes in hematological malignancies, as well as in healthy individuals with clonal hematopoiesis. Inflammatory stress is known to promote the expansion of Tet2-deficient hematopoietic stem cells, as well as the initiation of pre-leukemic conditions. Infection is one of the most frequent complications in hematological malignancies and antibiotics are commonly used to suppress infection-induced inflammation, but their application in TET2 mutation-associated cancers remained underexplored. In this study, we discovered that Tet2 depletion led to aberrant expansion of myeloid cells, which was correlated with elevated serum levels of pro-inflammatory cytokines at the pre-malignant stage. Antibiotics treatment suppressed the growth of Tet2-deficient myeloid and lymphoid tumor cells in vivo. Transcriptomic profiling further revealed significant changes in the expression of genes involved in the TNF- signaling and other immunomodulatory pathways in antibiotics-treated tumor cells. Pharmacological inhibition of TNF- signaling partially attenuated Tet2-deficient tumor cell growth in vivo. Therefore, our findings establish the feasibility of targeting pro-inflammatory pathways to curtail TET2 inactivation-associated hematological malignancies.

published proceedings

  • Cancer Lett

altmetric score

  • 1.5

author list (cited authors)

  • Zeng, H., He, H., Guo, L., Li, J., Lee, M., Han, W., ... Huang, Y.

citation count

  • 15

complete list of authors

  • Zeng, Hongxiang||He, Hailan||Guo, Lei||Li, Jia||Lee, Minjung||Han, Wei||Guzman, Anna G||Zang, Shengbing||Zhou, Yubin||Zhang, Xiaotian||Goodell, Margaret A||King, Katherine Y||Sun, Deqiang||Huang, Yun

publication date

  • January 2019