ArticleBlood neoplasia2025
Targeting HASPIN kinase disrupts SR protein-mediated RNA splicing and synergizes with BCL-2 inhibitor venetoclax in AML.
Article in Blood neoplasia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed.
- Review
- Drugging non-canonical kinases in cancer therapeutics: Molecular targets, underlying mechanisms and small-molecule inhibitors.Acta pharmaceutica Sinica. B · 2026Review
- Structural insights into selective recognition of ATP-mimicking inhibitors by the atypical kinase HASPIN.Scientific reports · 2026Article
- Splicing Factor Mutations in Chronic Myelomonocytic Leukemia: Biological Consequences and Therapeutic Implications.Current hematologic malignancy reports · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemia (AML) is a blood cancer complicated by acquired drug resistance, disease relapse, and low overall survival rates. Combination therapies using multiple targeted inhibitors have been effective in treating patients with AML. However, combination treatments are limited by the number of usable targets and our ability to create rational pairings using complimentary molecular mechanisms. Here, we used a human kinase domain-targeted CRISPR screen to identify histone H3-associated protein (HASPIN) kinase as a significant, understudied dependency in AML. HASPIN depletion significantly reduced growth rate, induced a cell cycle arrest, and dysregulated transcription in AML. A proteomics data mining study characterized serine and arginine repeat enriched splicing factors (SR proteins) as a major category of HASPIN kinase substrates and highlighted the role of HASPIN as a splicing regulatory kinase. Accordingly, HASPIN depletion strongly dysregulated splicing in AML cells. HASPIN inhibitor CHR-6494 effectively reduced cell viability across AML subtypes while sparing healthy cells. Furthermore, a novel combination therapy consisting of CHR-6494 and B-cell lymphoma 2 (BCL-2) inhibitor venetoclax synergistically reduced AML cell viability and resensitized venetoclax-resistant AMLs to treatment. Our study presents HASPIN kinase as a novel therapeutic target for AML, underscores an underappreciated role of HASPIN in splicing regulation, and proposes a viable combination treatment for clinical testing.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.