OBJECTIVE: To highlight the priorities in geriatric assessment research in myeloid malignancies and discuss design considerations necessary to ensure research is patient-centric, generalizeable, and high quality.
RESULTS: Older adults with myeloid malignancies including those who are perceived to have excellent performance status have multiple functional impairments. These impairments are associated with early mortality. Older adults have different functional trajectories through the course of treatment; this will be further investigated in our ongoing multicenter study. In a single-center study, we have demonstrated the use of geriatric assessment to guide treatment is feasible. Key priorities include designing a multicenter validation study to confirm the role of geriatric assessment in determining treatment tolerance and survival. Such a study should include core geriatric assessment measures and should enroll diverse patient population across various practices. Conducting such a study is necessary to advance patient care and trial design, and to open venues to conduct studies to confirm the role of geriatric assessment in treatment selection.

Acquired myeloid malignancies are a spectrum of clonal disorders known to be caused by sequential acquisition of genetic lesions in hematopoietic stem and progenitor cells, leading to their aberrant self-renewal and differentiation. The increasing use of induced pluripotent stem cell (iPSC) technology to study myeloid malignancies has helped usher a paradigm shift in approaches to disease modeling and drug discovery, especially when combined with gene-editing technology. The process of reprogramming allows for the capture of the diversity of genetic lesions and mutational burden found in primary patient samples into individual stable iPSC lines. Patient-derived iPSC lines, owing to their self-renewal and differentiation capacity, can thus be a homogenous source of disease relevant material that allow for the study of disease pathogenesis using various functional read-outs. Furthermore, genome editing technologies like CRISPR/Cas9 enable the study of the stepwise progression from normal to malignant hematopoiesis through the introduction of specific driver mutations, individually or in combination, to create isogenic lines for comparison. In this review, we survey the current use of iPSCs to model acquired myeloid malignancies including myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), acute myeloid leukemia and MDS/MPN overlap syndromes. The use of iPSCs has enabled the interrogation of the underlying mechanism of initiation and progression driving these diseases. It has also made drug testing, repurposing, and the discovery of novel therapies for these diseases possible in a high throughput setting.