Model for disease progression of CD38⁺ CLL cells. (A) Chemokines may generate molecular gradients that guide CD38⁺cells to CD31⁺stromal cells and thus initiate the CD38 signaling pathway. (B) CD38⁺ CLL cells can alternatively be attracted to CD31⁺ cells, which in turn synthesize and secrete survival chemokines. These mechanisms accumulate in CLL cells, leading to the progressive implementation and exasperation of signaling pathways, ultimately causing disease progression and eventually acute transformation. The y-axis shows disease progression, whereas the x-axis lists potentially confounding elements.