Bulk RNAseq of primary CD34+ HSPCs in Myeloproliferative neoplasms patients receiving tamoxifen

TAMARIN study is a Phase II, multicenter, single arm A'herns design clinical trial assessing tamoxifen's safety and activity in reducing molecular markers of disease burden in MPN.The primary outcome (=50% allele burden reduction at 24 weeks) was met by 3/37 patients; 5/37 additional patients showed =25% reductions. CD34+ HSPCs were collected from responders and non-respondersin the baseline line and 24W after tamoxifen treatment. RNAseq was performed to investigate the molecular signature about tamoxifen sensitivity and pharmacological mechanism of tamoxifen in MPN patients. Overall design: Eligibility criteria included MPN patients aged =60 years, with eligible women being post-menopausal (defined as amenorrhoeic for at least 12 consecutive months following cessation of all exogenous hormonal treatments); confirmed diagnosis of JAK2-V617F, CALR 5bp insertion (exon 9), or CALR 52bp deletion (exon 9) positive ET, PV or MF (primary or secondary) for = 6 months. Tamoxifen was provided at the common dose used in ER+ breast cancer (20 mg oral daily, progressively escalated to 40 mg daily upon good tolerance and when there was no hematological response or mutant allele burden reduction at 12w). All patients received trial treatment for 24 weeks. Treatment continuation was encouraged but not mandated after 24w for patients who did not experience persistent side effects greater than grade 1 or thrombotic events of any grade and that fulfilled one or more of the following criteria at 24 weeks: =25% reduction in allele burden compared to baseline; improvement of haematological response compared to baseline without changes in cytoreductive therapy dose according to 2009 ELN criteria for ET/PV patients and to IWG-MRT response criteria for MF patients; a decrease in requirement for cytoreduction without deterioration of haematological response compared to baseline according to 2009 ELN criteria for ET/PV patients and to IWG-MRT response criteria for MF patients. Their response was reassessed after 36 and 48 weeks of treatment as applicable.