Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0023418 (
leukemia
)
93,477
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Zinc finger protein 521
(
ZNF521
) is a multiple zinc finger transcription factor and a strong candidate as regulator of hematopoietic stem cell homeostasis. Recently, independent gene expression profile studies have evidenced a positive correlation between
ZNF521
mRNA overexpression and MLL-rearranged acute myeloid leukemia (AML), leaving open the question on the role of
ZNF521
in this subtype of
leukemia
. In this study, we sought to analyze the effect of
ZNF521
depletion on MLL-rearranged AML cell lines and MLL-AF9 xenograft primary cells. Knockdown of
ZNF521
with short-hairpin RNA (shRNA) led to decreased
leukemia
proliferation, reduced colony formation and caused cell cycle arrest in MLL-rearranged AML cell lines. Importantly, we showed that loss of
ZNF521
substantially caused differentiation of both MLL-rearranged cell lines and primary cells. Moreover, gene profile analysis in
ZNF521
-silenced THP-1 cells revealed a loss of MLL-AF9-directed leukemic signature and an increase of the differentiation program. Finally, we determined that both MLL-AF9 and MLL-ENL fusion proteins directly interacted with
ZNF521
promoter activating its transcription. In conclusion, our findings identify
ZNF521
as a critical effector of MLL fusion proteins in blocking myeloid differentiation and highlight
ZNF521
as a potential therapeutic target for this subtype of
leukemia
.
...
PMID:ZNF521 sustains the differentiation block in MLL-rearranged acute myeloid leukemia. 2841 27
