Expression of CD38. (A) The number of CD38⁺ cells in murine blood relates to CLL cell proliferation. At the first time point, CLL cells do not divide and the number of CD38⁺ leukemic cells is low. CD38-expressing CLL cells reach maximal levels at the second time point when CLL cells have divided, approximating that in donor patient's blood (solid line). (B) The percent of CD38-expressing cells in mouse blood correlates closely with that in patient's blood (10 CLL samples, 42 mice). Asterisks indicate experiments in which hCD34⁺ cells were administered. Note that the levels of CD38-expressing cells are similar between murine and human blood regardless of the system (hCD34⁺ cells or mature alloAPCs) used to permit CLL cell expansion in vivo. (C) Note that the activation states of CLL cells differ on the basis of anatomic location. Although there is considerable leukemic cell proliferation occurring in the spleen and 24.2% cells express CD38, there is negligible division occurring in PB, peritoneum, and BM. Data collected at death or time of sacrifice. (D) CLL (CD19⁺CD5⁺CFSE⁺) cells in the spleen far outnumber those in BM.