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CBX4 Facilitates the Development of Acute Monocytic Leukemia by Recruiting HDAC to Suppress Runx1.

Listed in NCBI GEO

Acute monocytic leukemia (AML-M5) is a type of acute myeloid leukemia, characterized by a dominance of monocytes in the bone marrow and peripheral blood.

Description

AML-M5 exhibits a poor prognosis compared to other AML subtypes, with a five-year long-term survival rate of less than 20% after diagnosis. Despite chromosomal aberrations and genetic mutations observed in AML-M5, its pathogenic mechanisms remain unclear.

In this study, we uncovered a distinct and heightened expression of CBX4, a core component of PRC1, in the peripheral blood of individuals diagnosed with AML-M5. By generating cbx4 overexpression transgenic and deleted mutant zebrafish lines, we observed elevated cbx4 expression in macrophages, selectively modulating their production during zebrafish hematopoiesis. Notably, aging zebrafish with cbx4 overexpression exhibited a progression to AML-M5-like hematopoiesis.

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Further mechanistic analyses revealed that Cbx4 regulates the fate of macrophage lineage by suppressing runx1 expression. This suppression is achieved through the recruitment of HDAC to the runx1 promoter via the region2 of cbx4, resulting in the down-regulation of the H3K27 acetylation level of runx1. These findings offer novel insights, providing potential avenues for risk assessment and molecular diagnosis of AML-M5 leukemia.

Moreover, CBX4 emerges as a promising target for the diagnosis and treatment of AML-M5 leukemia.

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Life Sciences
Provenance · 1 source records, 7 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE27919915 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:7955source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title