mercaptopurine

The current guideline describes the gene-drug interactions for TPMT, NUDT15 and thiopurines (azathioprine, 6-mercaptopurine and thioguanine). For TPMT or NUDT15 IM treated for leukaemia, starting with the normal dose can be considered and then decrease the dose to the advised dose described above in case toxicities occur. For NUDT15 PM reduced starting dose is advised only if an alternative is not possible, due to a higher uncertainty in the calculated dose reduction for NUDT15 PM than for TPMT PM.DPWG classifies genotyping for TPMT and NUDT15 "essential" before thiopurine initiation.

P2, N=355, Completed, Abivax S.A. | Phase classification: P2b --> P2 | N=254 --> 355

The thiopurines 6-mercaptopurine and 6-thioguanine (TG) are analogs of guanine and are used in the treatment of hematological malignancies and immune-mediated inflammatory diseases. dMeTG could also be detected in patient samples, although in low amounts and primarily in samples with high DNA-TG levels. The developed method for the quantitation of dMeTG and dTG can be used in further studies to investigate the role of DNA-MeTG in the mechanism of action of thiopurines, including its antileukemic efficacy and effects on acquired mutations.

Excessive 6-thioguanine (6-TGN) levels worsen neutropenia, while elevated 6-methylmercaptopurine (6-MMP) levels contribute to hepatotoxicity. In contrast, two variants in the IMPDH1 gene, rs2228075 and rs2278294, are correlated with more frequent neutropenia. These findings highlight novel genetic variants influencing 6-MP metabolism and toxicity in paediatric ALL patients.

HOXA5 plays a dual role in solid versus hematologic malignancies and serves as a key spatial immune regulator. It is a robust prognostic biomarker and therapeutic target in AML, with mercaptopurine representing a promising repurposing candidate.

P3, N=5949, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2025 --> Oct 2026

P2, N=53, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting | Trial completion date: Apr 2028 --> Mar 2029 | Trial primary completion date: Apr 2028 --> Mar 2029

P2, N=100, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed

Most patients with APL presented with fever and bleeding. The bcr1 transcript of PML-RARα was the most commonly observed. ATRA and ATO-based treatment was associated with high remission rates, manageable toxicity, and a low relapse rate.

Mercaptopurine (MP)-based maintenance therapy is essential to cure acute lymphoblastic leukemia (ALL). Dose escalation is unlikely to improve myelosuppression but will increase the risk of hepatotoxicity. Low-dose mercaptopurine combined with allopurinol can improve efficacy and reduce the risk of hepatotoxicity.

P3, N=847, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2025 --> Sep 2026

P2, N=39, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Aug 2025 --> Aug 2026 | Trial primary completion date: Aug 2025 --> Aug 2026