CIC in archived human lymphoma samples and TME models. (A) Pleural fluid (left) and lymph node biopsy (right) from a patient with lymphoplasmacytic lymphoma. Note the membrane of the outer cell in the LN biopsy (hard to see but discernable). Arrows highlight the CIC. (B) Pleural fluid from a patient with CLL. (C) Major steps in setting up TME models: (1-2) place collected human tissues with preseeded BMF; (3) add B-cell growth factors such as CpG/IL15 and drugs, coculture for 5 to 7 days or longer; and (4) perform assays with microscopy or flow cytometry. (D) UMAP of single cell genomics showing 11 cell clusters. (E) CLL cells under TME stimuli (CpG/IL-15) display increased MYC signature. (F) Cells divide into daughter cells; BMF only (Top); BMF+CpG/IL-15 (bottom). CFSE, Carboxyfluorescein Succinimidyl Ester; PB, peripheral blood; BM, bone marrow; UMAP, Uniform Manifold Approximation and Projection.