Highlighted research articles

Biomarkers predicting CAR T-cell (CAR T) therapy outcomes in myeloma remain to be established. In this prespecified analysis of the KarMMa trial, Paiva et al. show that persistent measurable residual disease (MRD) around the time of peak expansion correlates with primary resistance to idecabtagene vicleucel. Associations of outcomes with M-protein and circulating plasma cells over the 1-year course were distinct from their profiles following traditional myeloma treatments, highlighting the unique biological mechanism of CAR T therapy. The findings offer one of the first clinical guides to using biomarkers for tailoring salvage therapy following CAR T in myeloma.

See article, p. 365.

The hallmarks of cancer include deregulated cellular metabolism and epigenetic reprogramming. In this work, Toyoda et al. show that a viral oncogene encoded in human T-cell leukemia virus type 1 (HTLV-1), HTLV-1 bZIP factor (HBZ), upregulates TAp73 by its two molecular forms, HBZ RNA and HBZ protein, via distinct mechanisms. Consequently, TAp73 contributes to both the Warburg effect and epigenetic reprogramming in HTLV-1–infected cells via induction of MCT1/4 and EZH2, respectively. These signatures are commonly observed in multiple types of cancer, implying that they are promising targets for wide-spectrum anticancer strategies.

See article, p. 374.

Tumor-promoting inflammation is considered an enabling characteristic of oncogenesis across cancers, including myeloid malignancies, but the mechanisms and mediating cell types remain incompletely understood. By deciphering the predicted signaling between human and mouse bone marrow–resident stem cells or their neoplastic counterparts with the stromal cell component of the niche, Chen et al. identify inflammatory remodeling of both hematopoietic stem cell and stromal cells as determinants of hematopoietic repression of the bone marrow and clinical outcome in human acute myeloid leukemia (AML).

See article, p. 394.