Exon skipping truncates the PDZ domain of human erythroid p55 in a patient with chronic myeloid leukemia in acute megakaryoblastic blast crisis.

Human p55, the major palmitoylated protein associated with the cytoplasmic face of the erythrocyte membrane, is believed to modulate interactions between protein 4.1 and glycophorin C. It is the prototype of a newly described family of signaling molecules that includes hD1g, the human homologue of the Drosophila discs-large tumor suppressor protein. Chronic myeloid leukemia is characterized by transformation to a fulminating acute leukemia, heralded by evolution of the Philadelphia chromosome positive genotype (Ph +) to further abnormalities. RT-PCR of p55 mRNA from a patient with acute megakaryoblastic CML revealed a 69 base pair deletion in the PDZ domain, corresponding to exon 5 of the p55 gene. The deletion of constitutive exon 5 not only marks the first abnormality of the p55 cDNA in human disease but also the first abnormality of a PDZ domain in human disease and may represent another genetic abnormality associated with CML in blast crisis.