Anomalistic Signaling as a Possible Biochemical Explanation for Discordant Maturation in Chronic Myelogenous Leukemia (CML)

The 9;22 chromosomal translocation characteristic of CML results in a fused bcr/abl gene and an abnormal fusion protein, p210bcr / abl. Relative to normal c-abl, p210bcr/abl has elevated tyrosine kinase activity that is essential for its transforming activity. We recently reported a prominent 62 kDa GAP-associated P-tyr protein and 5 additional consistent but less prominent P-tyr proteins as well as 5 more minor P-tyr proteins that are constitutively tyrosine phosphorylated in primary primitive lineage negative (lin) chronic phase CML blasts but not in comparable primary lin-normal blasts. The GAP-associated p62 protein has now been purified, sequenced and its gene has been cloned; it is a previously unidentified protein and is currently being characterized.