RIBOSOME BIOGENESIS may represent a promising therapeutic target in acute myeloid leukaemia, according to new research showing that the ribosome associated factor MYBBP1A supports leukaemia cell growth through dual roles in protein synthesis and gene regulation.
Investigators analysed proteomic profiles from 55 patients with poor risk acute myeloid leukaemia and four normal myeloid samples. The analysis identified 1,646 proteins that were upregulated and 759 that were downregulated in the disease samples. Among the most significantly enriched pathways was ribosomal RNA processing, alongside cell cycle related pathways, highlighting the importance of ribosome biogenesis in the biology of acute myeloid leukaemia.
Ribosome Biogenesis Pathways Elevated in Acute Myeloid Leukaemia
The study found that several pathways linked to ribosome biogenesis, including ribosomal RNA processing, synthesis, and ribosomal subunit maturation, were increased across many molecular subtypes of acute myeloid leukaemia. However, this enrichment was not observed in certain genetic subtypes including those with IDH1 or IDH2, SRSF2, or NPM1 mutations.
Researchers then focused on MYBBP1A, a ribosome biogenesis factor significantly upregulated in the proteomic dataset (fold change: 2.3; false discovery rate=1.11×10⁻¹¹). Although MYBBP1A has previously been described as a tumour suppressor in several solid cancers, its function in acute myeloid leukaemia has remained unclear.
Immunoblot analysis confirmed elevated MYBBP1A protein levels in primary patient samples and 11 acute myeloid leukaemia cell lines compared with normal cord blood haematopoietic stem and progenitor cells and bone marrow cells.
MYBBP1A Supports Leukaemia Cell Growth
Functional experiments demonstrated that depletion of MYBBP1A in human acute myeloid leukaemia cell lines using RNA interference and CRISPR Cas9 approaches significantly reduced cell proliferation while increasing apoptosis and promoting myeloid differentiation. In mouse transplantation models, animals receiving MYBBP1A depleted leukaemia cells showed significantly improved survival compared with controls.
Similarly, genetic knockout of Mybbp1a in murine leukaemia models delayed disease development, extending median survival from 32 days in wild type animals to 137 days in knockout mice.
Dual Role in Protein Synthesis and Cell Cycle Control
Mechanistic studies revealed that MYBBP1A localises to the nucleolus and interacts with ribosomal proteins and ribosome biogenesis factors including fibrillarin. Loss of MYBBP1A disrupted recruitment of fibrillarin to the nucleolus and reduced production of multiple ribosomal RNA species including 47S, 5.8S, 18S, and 28S ribosomal RNA.
This disruption led to reduced global protein synthesis, as demonstrated by polysome profiling and translation assays. Proteomic analysis further revealed that MYBBP1A regulates components of the DNA unwinding complex MCM2–7, which are critical for cell cycle progression.
Chromatin immunoprecipitation sequencing confirmed that MYBBP1A binds directly to promoters of MCM genes, and loss of the factor reduced expression of MCM6 and MCM7. As a result, leukaemia cells lacking MYBBP1A were arrested in the G1 phase of the cell cycle.
Together, these findings suggest that ribosome biogenesis is widely deregulated in acute myeloid leukaemia and identify MYBBP1A as a key regulator supporting leukaemia cell survival through both ribosome production and transcriptional control of cell cycle genes.
Reference
To P et al. Investigating ribosome biogenesis in AML identifies MYB-binding protein 1A (MYBBP1A) as an essential regulator of leukemia cells. Abstract 990. ASH Congress, 6-9 December 2025.
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