Statin use in myelodysplastic syndromes is associated with a better survival and decreased progression to leukemia

Afzal, Amber; Fiala, Mark A.; Jacoby, Meagan A.; Walter, Matthew J.

doi:10.1182/bloodadvances.2023009818

Cited by 2 publications

(2 citation statements)

References 15 publications

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“…PSM analysis showed improved survival and decreased progression to acute myeloid leukemia among statin users. 39 Our study of MPN patients showed that statin use was associated with better survival as it reduced the risk of all‐cause mortality by about 22%.…”

Section: Discussionmentioning

confidence: 78%

Statin use, survival and incidence of thrombosis among older patients with polycythemia vera and essential thrombocythemia

Podoltsev,

Wang,

Shallis

et al. 2023

Cancer Medicine

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BackgroundPolycythemia vera (PV) and essential thrombocythemia (ET) are linked to increased risk of cardiovascular morbidity and mortality. In addition to the reduction in of arterial thrombotic events, statins may prevent venous thrombosis including among patients with cancer. As previous registry‐ and claims‐based studies revealed that the use of statins may improve the survival of patients with various malignancies we evaluated their impact on outcomes of older adults with PV and ET.MethodsWe identified 4010 older adults (aged 66–99 years at diagnosis) with PV (n = 1809) and ET (n = 2201) in a population‐based cohort study using the Surveillance, Epidemiology, and End Results‐Medicare database with median follow‐up of 3.92 (interquartile range: 2.58–5.75) years. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) approaches were utilized to assess potential association between statins and overall survival. Multivariable competing risk models with death as a competing risk were used to evaluate possible relationship between statins and the incidence of thrombosis.Results55.8% of the patients used statins within the first year after PV/ET diagnosis, and statin use was associated with a 22% reduction in all‐cause mortality (PSM: hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.63–0.98, p = 0.03; IPTW: HR = 0.79, 95% CI: 0.64–0.97, p = 0.03). Statins also reduced the risk of thrombosis in this patient population (PSM: HR = 0.63, 95% CI: 0.51–0.78, p < 0.01; IPTW: HR = 0.57, 95% CI: 0.49–0.66, p < 0.01) as well as in PV and ET subgroups.ConclusionsThese findings suggest that it may be important to incorporate statins into the therapeutic strategy for older adults with PV and ET.

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Section: Discussionmentioning

confidence: 78%

Statin use, survival and incidence of thrombosis among older patients with polycythemia vera and essential thrombocythemia

Podoltsev,

Wang,

Shallis

et al. 2023

Cancer Medicine

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“…Encouragingly, a recent retrospective analysis of MDS patients (including some HMA-treated high-risk cases) reported improved survival and reduced progression to AML for patients who commenced statin treatments three months before or after MDS diagnosis 63 . Current clinical trials are testing the safety of a statin (pitavastatin) in combination with AZA and venetoclax in AML patients 64 and our results imply that DAC and statin co-treatments should also be assessed.…”

Section: Discussionmentioning

confidence: 99%

Upregulated cholesterol biosynthesis facilitates the survival of methylation-retaining AML cells following decitabine treatment

Bond,

Burnard,

Uddipto

et al. 2024

Preprint

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DNA hypomethylating agents (HMAs) are used to treat acute myeloid leukaemia (AML) and myelodysplasia patients who are unsuitable for intensive chemotherapy, but low response rates and therapy-resistant relapse remain significant challenges. To optimise HMA efficacy, we must understand how resistance and relapse arise from cells that survive treatment. Here we combine single-cell multi-omic analysis with parallel colony-forming assays to link HMA-induced molecular heterogeneity with functional consequences in AML cells. HMAs, azacytidine (AZA) and decitabine (DAC), induced global epigenetic heterogeneity associated with upregulation of inflammatory responses and cell death pathways in a subset of hypomethylated cells. Some AML cells maintained high DNA methylation during treatment, and these methylation-retaining cells had increased self-renewal capacity following DAC, but not AZA. Molecular profiling of individual colonies revealed upregulated cholesterol biosynthesis as an adaptation to HMA treatment, and inhibition by rosuvastatin enhanced DAC effects in vitro and in vivo. Thus, HMA-induced heterogeneity has important implications for AML cell growth and statins are a candidate co-treatment strategy to delay or prevent HMA-resistant relapse.

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Statin use in myelodysplastic syndromes is associated with a better survival and decreased progression to leukemia

Cited by 2 publications

References 15 publications

Statin use, survival and incidence of thrombosis among older patients with polycythemia vera and essential thrombocythemia

Statin use, survival and incidence of thrombosis among older patients with polycythemia vera and essential thrombocythemia

Upregulated cholesterol biosynthesis facilitates the survival of methylation-retaining AML cells following decitabine treatment

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