Interestingly, ERK1/2 signaling emerged as a key hub in CXCR4 signaling downstream of WHIM-mutated variants, consistently with the reported ERK1/2 signaling dysfunction that has already been observed in CXCL12-activated leukocytes or cell lines carrying CXCR4 WHIM-mutated variants R334X and S338X in both WHIM and Waldenström macroglobulinemia patients (32). Here, MAPK3 is linked to Waldenstrom macroglobulinemia.