THPO and B-cell chronic lymphocytic leukemia: Several next generations of humanized mouse strains such as NRG (NOD-Rag2-IL2rgTm1/Rj) and NRGS (NRG-SGM3) mice (100), MISTRG mice (expressing human M-CSF, IL-3/GM-CSF, and THPO) (101), and MISTRG-6 (MISTRG with an additional knock-in of the human IL-6 allele) (102) that express human cytokines supporting the engraftment of human HSCs, myeloid cells, and NK cells might enable the generation of CLL mouse models that give a full-blown disease and allow the dissection of the impact of the TME in vivo.