In pathological conditions with concurrent neutrophilia, modifications of erythrocyte membrane proteins are reported. In chronic\r\nmyeloid leukemia (CML), amyeloproliferative disease wherein neutrophilia is accompanied by enhanced erythrophagocytosis, we\r\nreport for the first time excessive cleavage of erythrocyte band 3. Distinct fragments of band 3 serve as senescent cell antigens\r\nleading to erythrophagocytosis. Using immunoproteomics, we report the identification of immunogenic 43 kDa fragment of band\r\n3 in 68% of CML samples compared to their detection in only 38% of healthy individuals. Thus, excessive fragmentation of band\r\n3 in CML, detected in our study, corroborated with the eryptotic phenotype. We demonstrate the role of neutrophilic cathepsin\r\nG, detected as an immunogen on erythrocyte membrane, in band 3 cleavage. Cathepsin G from serum adsorbs to the erythrocyte\r\nmembrane to mediate cleavage of band 3 and therefore contribute to the eryptotic phenotype in CML.
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