NOTCH1 and B-cell chronic lymphocytic leukemia: The importance of microenvironmental signals in inducing NOTCH1 cascade is further documented by the evidence that CLL cells in the lymph nodes frequently express NOTCH1-ICD independent of NOTCH1 mutation (69, 131), especially within the proliferation centers, which represent the key microanatomical sites where CLL cells interact with accessory cells and acquire chemoresistance.