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ASH 2020 | Effects of tamoxifen on the mutant allele burden in MPNs

Claire Harrison, MD, DM, FRCP, FRCPath, Guy’s and St Thomas’ NHS Foundation Trust, London, UK, shares the findings of the TAMARIN study (ISRCTN65011803): A Phase II trial of tamoxifen’s safety and ability to reduce molecular markers of disease burden in patients with myeloproliferative neoplasms (MPNs). Preclinically, estrogen receptor modulation has been shown to normalize apoptosis in JAK2-mutant hematopoietic progenitors, a common causative mutation of MPNs. Therefore, mutant allele burden was measured after 12 and 24 weeks of tamoxifen therapy. The results showed that of 32 patients completing 24 weeks of treatment, 4 patients achieved ≥50% reduction in mutant allele burden, with an additional 6 reaching ≥25% reduction. Baseline analysis of the hematopoietic stem and progenitor cell transcriptome completely segregated treatment responders and non-responders, indicating that clinical benefit could be predicted. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.