What type of study is this?

This is a Experimental Study study (also classified as: In Vitro Study, Validation Study).

What question did this study set out to answer?

The study aims to understand how germline noncoding variants impact clonal hematopoiesis and contribute to myeloid malignancies.

December 8, 2025Blood

View Full Paper

Ask AI

Bookmark

Authors

Genome wide association studies reveal risk variants affecting clonal hematopoiesis, suggesting new avenues for targeting myeloid malignancies.

The study aims to understand how germline noncoding variants impact clonal hematopoiesis and contribute to myeloid malignancies.
Utilized a massively parallel reporter assay (MPRA) to screen non-coding variants.
Searched for appropriate cell types, identifying MUTZ-3 as a model for HSCs.
Performed lentiviral MPRA screen using a library of ~73,000 constructs in MUTZ-3 cells.
Conducted individual reporter assays to confirm enhancer activity of identified variants.
Executed CRISPR/Cas9 experiments for functional validation of enhancer activity.
Identified several noncoding variants with allele specific reporter activity in clonal hematopoiesis.
Prioritized rs17834140 variant for further studies, located within the MSI2 gene's enhancer region.
Confirmed that the risk allele increases MSI2 expression, influencing hematopoiesis.
MSI2 overexpression improved colony replating in TET2 knockout HSCs, indicating a role in clonal expansion.

Shekhar et al. (2025) studied this question.

View Full Paper

Ask AI

Bookmark

Genome wide association studies reveal risk variants affecting clonal hematopoiesis, suggesting new avenues for targeting myeloid malignancies.