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Nat Commun: lncRNA HOXBLINC promotes the occurrence of acute myeloid leukemia with NPM1 mutation

 Last Update: 2021-04-14
 Source: Internet
 Author: User

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NPM1 is the most commonly mutated gene in acute myeloid leukemia (AML).

Mutations in NPM1 lead to incorrect cytoplasmic localization of the mutant protein (NPM1c+), which is also crucial for its role in the development of leukemia.

NPM1c+ can maintain a unique leukemia gene expression program, which is characterized by activating the HOXA/B cluster and MEIS1 oncogene, and promotes the occurrence of leukemia.

In this study, the researchers found that the activation of long non-coding RNA (lncRNA) HOXBLINC is a key downstream mediator of the NPM1c+-related leukemia transcription program and the occurrence of leukemia.

The activation of long non-coding RNA (lncRNA) HOXBLINC is a key downstream mediator of the NPM1c+-related leukemia transcription program and the occurrence of leukemia.

HOXBLINC is activated in NPM1c+AML patients

In addition, overexpression of HoxBlinc (HoxBlincTg) in the mouse model can enhance the self-renewal ability of hematopoietic stem cells (HSC) and enhance the production of bone marrow, which leads to the occurrence of AML-like diseases.

stem cell

Overexpression of HoxBlinc induces AML in mice

Mechanism studies have shown that HoxBlinc regulates the activation of these genes in HoxBlincTg HSPC by recruiting NLL1, binding to the promoter region of NPM1c+ related genes and modifying H3K4me3.

org/10.

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