Intrafemoral xenograft model reproduces lymphoma BM niche. (A) Tumor cell dissemination. Evolution over time of the proportion of viable human tumor cells (DAPI^–hCD20⁺) compared with viable murine CD45⁺ cells in the blood (red), spleen (blue), and BM (grafted femur in green and contralateral femur in orange) of Rag^−/−γc^−/− mice that were transplanted with 0.5 × 10⁶ DOHH2 cells by intrafemoral route (left). Luciferase imaging of representative mouse from 14 to 42 days after engraftment. Green star indicates grafted femur, and purple star indicates contralateral femur (right). (B) Experimental design of the B-cell and stromal cell transcriptomic characterization in Rag^−/−γc^−/− mice untreated, injected with PBS (sham), or grafted with DOHH2. (C) Using gene set enrichment analysis, enrichment for pathways upregulated in published data of primary FL B cells (FL) vs centrocytes²⁴ were investigated in published data of DOHH2 cocultured with tonsil stromal cells and ECM in DT3D vs classical D2D²⁵ and in DOHH2 recovered at the late time point (day 40) and/or at the early time point (day 19). Circle colors depict the NES and circle sizes the FDR (left). Spearman correlation plot of comparisons using NES values from previously selected pathways (right). ∗P < .05. CC, centrocytes; D, day; D2D, 2-dimensional DOHH2 culture; DT3D, 3-dimensional spheroids with tonsil stromal cells; FDR, false discovery rate; hCD20, human CD20; mCD45, murine CD45; max, maximum; min, minimum; NES, normalized enrichment score; q.val, q value.