We will focus on CXCR4 since it represents the most widely expressed chemokine receptor in human malignancies and it is a crucial player in the plasticity and alteration of the TME both in hematologic tumors, such as multiple myeloma, acute myeloid leukemia, T cell acute lymphoblastic leukemia (T-ALL), and in solid tumors such as ovarian, prostate, colon, brain, breast, and bladder cancer (74–76). This evidence concerns the gene CXCR4 and acute lymphoblastic leukemia.