Figure 4.

Pedigree of the final FL cell evolution of patient 3 – synopsis of compartment-specific and inter-compartment pedigrees. Among the entire clonal population of patient 3 the least mutated sequenced clones were clone m2 of the initial lymph node (LN) population of 2004 and clone ×3 of the first relapse population of the bone marrow (BM) of year 2006. Interestingly both clones shared an identical mutation pattern suggesting a migratory link between the LN and the BM compartments. Considering the generated HPC, and the probability measure (pm)-values obtained for the compartment-specific and the inter-compartment populations, an initial inter-compartment migration in 2004 was a plausible option for clonal evolution, since the initial migration was directed from the LN to the BM where a HPC (BM1-04) included the mutation pattern of clone m2, which thus constituted the most likely “founder clone” of the clonal BM population. By detection of clone ×3 among the BM clones of the first relapse in 2006 showing identical mutations with the inital nodal clone m2, and the inclusion of this very mutation pattern in the HPC “founder clone” of the BM-population of 2004 (BM1 04) and the most likely HPC “founder clone” of the second BM relapse population of 2007 (BM1 07), BM persistence during therapy was evident. Chronological analysis of the different populations (not shown in detail), showed that the LN was reinfiltrated from the BM. Reinfiltration of the LN compartment of 2007 from the BM was more likely than nodal persistence during the interval from the 2004 to 2007 (Online Supplementary Tables S4F–H). However, whether reinfiltration took place in 2004, 2006 or 2007 could not be determined. Blue lines represent putative clonal migratory events from the LN to the BM compartment, red lines represent migration in the opposite direction (i.e. putative clonal migratory events from the BM to the LN compartment).