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Environmental or self-antigens and homotypic interactions cause BCR and Toll-like receptor (TLR) signaling, amplifying the response of CLL cells to other signals within the microenvironment and escalating the activation of anti-apoptotic and proliferation pathways.31,32 Genomic experiments have determined recurrent mutations in genes regulating tumor mobile-microenvironment interactions, which might be already required for tumor cell expansion. So, NOTCH1 mutations are dependent on the presence of Notch ligands within the microenvironment and activate procedures including mobile migration, invasion and angiogenesis.

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