Issues
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Cover Image
By testing patient cancer cell sensitivity to hundreds of drugs, functional precision medicine (FPM) holds promise to prospectively identify individualized treatments. Two studies in this issue take FPM to new frontiers. Wang, Chan, Cheng, Ng and colleagues (page 516) combined FPM with genome and RNA sequencing to create pharmacogenomic data sets of acute myeloid leukemia (AML), the first for pediatric AML (of any ethnicity) and for Asian adult AML (of any age). The pharmacogenomic approach guided clinical decisions, resulting in a remission in two evaluable cases. The high-dimensional data set uncovered gene-drug interactions, validated in xenografts as therapeutic vulnerabilities. Heinemann, Kornauth and colleagues (page 502) improve accuracy and scalability of FPM by deploying a neural network to score FPM drug screen results based on cell morphology rather than lineage markers. In a retrospective analysis, the approach outperformed clinician-based recommendations in the EXALT clinical trial. For more information, see the corresponding articles at the page numbers listed above. - PDF Icon PDF LinkTable of Contents
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Editorial
The AACR Journals: Advancing Progress Toward the AACR's 115-Year Mission
In This Issue
In the Spotlight
Research Briefs
Anti-spike T-cell and Antibody Responses to SARS-CoV-2 mRNA Vaccines in Patients with Hematologic Malignancies
Combined anti-spike TCR repertoire and antibody titers reveal differential T- and B-cell responses in a large cohort of patients with B-cell malignancies after 2 and 3 doses of SARS-CoV-2 mRNA vaccines.
Changes in Bone Marrow Tumor and Immune Cells Correlate with Durability of Remissions Following BCMA CAR T Therapy in Myeloma
High-dimensional analysis of the tumor microenvironment identifies determinants of durable responses following CAR T therapy in myeloma.
Deep Morphology Learning Enhances Ex Vivo Drug Profiling-Based Precision Medicine
A computational method improves personalized medicine screening that looks for the best therapy for individual patients across hematologic malignancies.
Research Articles
Pharmacogenomic Profiling of Pediatric Acute Myeloid Leukemia to Identify Therapeutic Vulnerabilities and Inform Functional Precision Medicine
The functional genomic landscape of pediatric AML is mapped through multimodal drug, genomic, and transcriptomic profiling, and translated into clinical application for precision medicine.
Progenitor Hierarchy of Chronic Myelomonocytic Leukemia Identifies Inflammatory Monocytic-Biased Trajectory Linked to Worse Outcomes
Single-cell progenitor hierarchy at CMML identifies a monocytic-biased trajectory associated with disease progression, expanded by inflammation, and diminished by hypomethylation therapy.
Targeting the EIF2AK1 Signaling Pathway Rescues Red Blood Cell Production in SF3B1-Mutant Myelodysplastic Syndromes With Ringed Sideroblasts
SF3B1-mutant MDS-RS is associated with buildup of erythroid progenitor cells upregulating EIF2AK1-associated heme deficiency response and autophagy genes. Targeting EIF2AK1 relieves the dysregulated progenitor phenotype.
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