TRIB2 regulates the differentiation of MLL-TET1 transduced myeloid progenitor cells

被引：3

作者：

Kim, Hyeng-Soo ^{[1
,2
]}

Oh, Seung Hwan ^{[3
]}

Kim, Ju-Heon ^{[1
]}

Sohn, Wern-Joo ^{[4
]}

Kim, Jae-Young ^{[4
]}

Kim, Do-Hyung ^{[5
]}

Choi, Sang-Un ^{[6
]}

Park, Kwon Moo ^{[7
]}

Ryoo, Zae Young ^{[1
]}

Park, Tae Sung ^{[8
]}

Lee, Sanggyu ^{[1
]}

机构：

[1] Kyungpook Natl Univ, Sch Life Sci, Plus KNU Creat BioRes Grp BK21, Daegu 41566, South Korea

[2] Kyungpook Natl Univ, Inst Life Sci & Biotechnol, Daegu 41566, South Korea

[3] Inje Univ, Dept Lab Med, Coll Med, Busan 47392, South Korea

[4] Kyungpook Natl Univ, Sch Dent, Dept Biochem, IHBR, Daegu 41940, South Korea

[5] Kyungpook Natl Univ, Dept Phys, Daegu 41566, South Korea

[6] Korea Res Inst Chem Technol, Daejeon 34186, South Korea

[7] Kyungpook Natl Univ, Sch Med, Dept Anat, Daegu 41944, South Korea

[8] Kyung Hee Univ, Sch Med, Dept Lab Med, Seoul 02447, South Korea

来源：

JOURNAL OF MOLECULAR MEDICINE-JMM | 2018年 / 96卷 / 11期

基金：

新加坡国家研究基金会;

关键词：

Leukemia; MLL-TET1; MLL; TET1; Trib2; ACUTE MYELOGENOUS LEUKEMIA; C/EBP-ALPHA EXPRESSION; H3K79; METHYLATION; MLL; PROTEIN; GENE; DNA; TANDEM; CEBPA; TET1;

D O I：

10.1007/s00109-018-1700-3

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The function and mechanism of action of MLL-TET1 (MT1) fusion protein in hematological cells are unclear and require further investigation. In the present study, we found that the MT1 fusion protein attenuated the expression of Cebpa, Csf1r, and Cd11b and inhibited the differentiation of myeloid progenitor cells. Increased binding of the MT1 fusion protein to the Trib2 promoter upregulated Trib2 mRNA and protein expression and downregulated Cebpa expression. Trib2 knockdown relieved the inhibition of myeloid cell differentiation induced by the MT1 fusion protein. Thus, TRIB2 is important for the survival of leukemia cells during MT1-related leukemogenesis and is important in maintaining differentiation blockade of leukemic cells.Key messages center dot MLL-TET1 fusion decreases the 5-hmC levels in the myeloid progenitor cells.center dot MLL-TET1 fusion inhibits myeloid differentiation through decreased expression of Cebpa.center dot MLL-TET1 fusion blocks the differentiation of the myeloid progenitor cells by overexpressing Trib2.center dot Knockdown of Trib2 in MLL-TET1 transduced cells induces myeloid differentiation.

引用

页码：1267 / 1277

页数：11

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