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Hematopoietic cell transplantation (HCT) is the only potentially curative treatment option for many patients with hematologic malignancies. While HCT outcomes have improved drastically over the years, patients and clinicians continue to face numerous survivorship challenges, such as relapse, graft-versushost disease, and secondary malignancies. Recent literature suggests that clonal hematopoiesis (CH), the presence of a recurrent somatic mutation in hematopoietic cells, in HCT patients or donors may be associated with outcomes in autologous and allogeneic HCT. Herein, we perform a review of the literature and summarize reported associations between CH and clinical outcomes in HCT. For commonly reported outcomes, we used meta-analysis methods to provide estimates of effect sizes when combining results. A total of 32 articles with relevant and independent contributions were included, covering both autologous (n = 19) and allogeneic (n = 13) HCT. The articles report variable risk for developing outcomes according to CH characteristics, patient disease status, and method of HCT. Using meta-analysis of available results, HCT outcomes with statistically significant effects by CH status include therapy-related myeloid neoplasms (OR 3.65, 95%CI 2.18-6.10) and overall survival (HR 1.38, 95%CI 1.20-1.58) in autologous HCT and relapse (HR 0.80, 95%CI 0.68-0.94) in allogeneic HCT. However, heterogeneity, biases, and limitations in the literature provide challenges for informing the translation of CH to clinical decision-making. We conclude with a call to action and discussion of next steps to build upon the current literature and provide granularity to the true clinical impact of CH in the setting of HCT.

Super enhancers (SE), large genomic elements that activate transcription and drive cell identity, have been found with cancer-specific gene regulation in human cancers. Recent studies reported the importance of understanding the cooperation and function of SE internal components, i.e., the constituent enhancers (CE). However, there are no pan-cancer studies to identify cancer-specific SE signatures at the constituent level. Here, by revisiting pan-cancer SE activities with H3K27Ac ChIP-seq datasets, we report fingerprint SE signatures for 28 cancer types in the NCI-60 cell panel. We implement a mixture model to discriminate active CEs from inactive CEs by taking into consideration ChIP-seq variabilities between cancer samples and across CEs. We demonstrate that the model-based estimation of CE states provides improved functional interpretation of SE-associated regulation. We identify cancer-specific CEs by balancing their active prevalence with their capability of encoding cancer type identities. We further demonstrate that cancer-specific CEs have the strongest per-base enhancer activities in independent enhancer sequencing assays, suggesting their importance in understanding critical SE signatures. We summarize fingerprint SEs based on the cancer-specific statuses of their component CEs and build an easy-to-use R package to facilitate the query, exploration, and visualization of fingerprint SEs across cancers.

Abstract Background The intersection of cancer and aging is an emerging public health challenge in developed countries because of the aging and expansion of the population. Aims We convened a panel of experts to share their insights on this topic at the inaugural University of Florida Health Cancer Center's (UFHCC's) Cancer and Aging Symposium, which was held virtually in February 2022. Methods We featured presentations from four leading scientists, whose research spans multiple disciplines including basic science, translational research, geriatric oncology, and population science. Results Each speaker offered their unique perspective and insight on the intersection between cancer and aging and discussed their current and ongoing research in this field. In addition to this panel of experts, scientists from the National Institutes of Health and the National Cancer Institute, as well as a UFHCC‐affiliated citizen scientist, shared their perspectives on strategies to move the field forward. Some of the key open questions and opportunities for future research offered by these presenters in aging and cancer include but are not limited to infusing health disparities research into the field of cancer and aging, assessing the value of geriatric assessment in identifying early vulnerabilities that may affect response to emerging cancer therapies in older patients, and assessing biological age and other biomarkers (e.g., clonal hematopoiesis) in relation to clinical endpoints and the development of primary, secondary, and tertiary cancer prevention interventions. Conclusion Research is needed to accelerate knowledge regarding the dynamic interplay of cancer and aging and optimize care in diverse older adults to achieve equity in cancer outcomes.