CLL cells are moved by the MARCKS brothers

In this issue of Blood, Beckmann et al(1) compare a proteomic screen of chronic lymphocytic leukemia (CLL) cells isolated from patients with mutated immunoglobulin heavy-chain variable region (IGHV) (M-CLL) to unmutated IGHV (UM-CLL). Among differentially expressed proteins, they found myristoylated alanine-rich C-kinase substrate (MARCKS) to be highly expressed in M-CLL patients, and low in patients with UM-CLL. They convincingly link the expression and phosphorylation of MARCKS to CLL cell migration (ie, key CLL signaling pathways, especially CXCR4 and B-cell receptor [BCR] signaling). They also corroborate the findings in samples from patients receiving treatment with the Bruton tyrosine kinase (BTK) inhibitor acalabrutinib.

Automated summary

The study reveals that MARCKS protein is differentially expressed in patients with chronic lymphocytic leukemia based on the mutation status of IGHV, and its expression and phosphorylation are linked to CLL cell migration through key signaling pathways. The findings were also confirmed in samples from patients treated with the BTK inhibitor acalabrutinib.