Abstract Background Hematologic malignancies exhibit marked biological heterogeneity that is often insufficiently characterized by genomic profiling alone. Integrated multi-omics approaches are required to enable more accurate prognostic stratification, elucidate resistance mechanisms, and identify therapeutic vulnerabilities across lymphoma, leukemia, and plasma cell neoplasms. Methods SCRUM-Japan MONSTAR3 is a nationwide, prospective, integrated multi-omics platform. The hematology cohort aims to enroll 400 patients with newly diagnosed or relapsed/refractory hematologic malignancies. Tumor specimens—including bone marrow aspirates/biopsies or lymph node tissues—are collected at diagnosis and at relapse. The multi-omics workflow encompasses whole-exome sequencing, whole-transcriptome sequencing, spatial transcriptomics, plasma proteomics, metabolomics, microbiome analysis, and tumor-informed measurable residual disease (MRD) monitoring. MRD is assessed using next-generation sequencing-based immunoglobulin heavy (IgH) and T-cell receptor (TCR) rearrangement analysis for lymphoid malignancies and whole-genome sequencing–based variant tracking for myeloid malignancies. Results Patient enrollment began in December 2024, followed by nationwide multicenter activation in November 2025. Multi-omics analyses have been implemented in a stepwise manner. Early operational indicators, including biospecimen acquisition, data quality control, and initiation of molecular assays, demonstrate the feasibility of coordinated nationwide deployment of this complex platform. Conclusion The MONSTAR3 hematology cohort represents the first nationwide integrated multi-omics initiative dedicated to hematologic malignancies. Its large scale, standardized biospecimen framework, and capacity to incorporate emerging technologies provide a robust infrastructure for molecular stratification, longitudinal disease monitoring, and hypothesis-driven interventional research, thereby advancing clinically actionable precision hematology.
Matsuda et al. (Sat,) studied this question.