Home Medizin RBM5 wurde als Schlüsselregulator von HOXA9 bei akuter myeloischer Leukämie identifiziert

RBM5 wurde als Schlüsselregulator von HOXA9 bei akuter myeloischer Leukämie identifiziert

von NFI Redaktion


Research conducted at St. Jude Children’s Research Hospital has uncovered a potential strategy for combating acute myeloid leukemia (AML), a type of blood cancer associated with poor prognosis. The overexpression of the protein HOXA9, found in over 70% of AML cases, has been a challenging target due to its role as a transcription factor. However, a study published in Genombiology has highlighted a promising alternative approach to tackling this protein.

Scientists utilized CRISPR/Cas9 screening to identify RBM5 and establish a causal link between RBM5 expression and leukemia cell proliferation. The study reveals a novel dual role of RBM5 as a DNA and RNA handler in gene expression, suggesting its potential as a therapeutic target.

Dr. Chunliang Li, a co-author of the study, explains, „This represents an ongoing effort since the inception of my laboratory in 2017. We established a unique reporter system in early 2019, which is the first reporter that authentically represents HOXA9 expression in these leukemia systems.“

– Chunliang Li, PhD, St. Jude Department of Tumor Cell Biology

This innovative approach involved attaching a fluorescent marker to the HOXA9 gene and inserting it into leukemia cell lines, enabling researchers to track differences in expression levels by observing fluorescence in cells. Through an unbiased CRISPR screening of the entire genome, various targets of HOXA9 were identified, with splice factors being the most prevalent pathway.

RBM5, an RNA-binding protein, emerged as a key player in the regulation of HOXA9 expression. The study unveils the critical DNA and RNA binding sites of RBM5 for its oncogenic functions. Remarkably, the absence of RBM5 in leukemia cells led to a significant reduction in HOXA9 mRNA levels, highlighting its potential as a therapeutic target for AML treatment.

Authors and Funding

The study was led by Mengli Zhang of Soochow University, with additional contributions from researchers at St. Jude and other collaborating institutions. Originally supported by grants from ALSAC, the fundraising and awareness organization of St. Jude, the study sheds light on a promising avenue for future AML therapies.

Source:

St. Jude Children’s Research Hospital

Journal reference:

Zhang, M., et al. (2024) The RNA-binding protein RBM5 plays an essential role in acute myeloid leukemia by activating the oncogenic protein HOXA9. Genombiology. doi.org/10.1186/s13059-023-03149-8.

Related Posts

Adblock Detected

Please support us by disabling your AdBlocker extension from your browsers for our website.