SCRUM-Japan MONSTAR3 hematology cohort: a nationwide multi-omics integrated platform for next-generation precision medicine in hematologic malignancies

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.