Selective expression and constitutive phosphorylation of Src-homology-2 and collagen-homology domains proteins in the CD34(+) fraction of chronic myelogenous leukemias
A. Bonati et al., Selective expression and constitutive phosphorylation of Src-homology-2 and collagen-homology domains proteins in the CD34(+) fraction of chronic myelogenous leukemias, CANCER RES, 60(3), 2000, pp. 728-732
The BCR/ABL fusion protein is a constitutively active tyrosine kinase that
is responsible for the pathogenesis of chronic myelogenous leukemia (CML),
Clinically, CML is characterized by a chronic phase (CP) that eventually te
rminates into a blast crisis (BC), BC transformation is associated with acc
umulation of CD34(+) blasts. We investigated the expression and phosphoryla
tion of Src-homology-2 and collagen-homology domains (Shc) proteins in subp
opulations of CML primary cells. Shc polypeptides are tyrosine kinase subst
rates that are constitutively tyrosine-phosphorylated in continuous cell li
nes of CML origin. High levels of Shc expression were found in the CD34(+)
cells from CML-BC, CML-CP and normal bone marrow, In contrast, CD34(-) frac
tions from CML-CP and normal bone marrow expressed low levels of p46(Shc).
Shc proteins were constitutively phosphorylated in the CD34(+) fractions fr
om CML cells (both CP and BC), but not in normal CD34(+) cells. These data
bear implications for the role of Shc in normal hemopoiesis and CML leukemo
genesis: (a) dramatic changes of Shc expression during terminal differentia
tion of hemopoietic cells adds a further level of regulation to the signal
transduction function of Shc; and (b) constitutive Shc tyrosine-phosphoryla
tion in the rare CD34(+) cells of CML-CP might contribute to the selection
of this subpopulation during the blast crisis transformation of CMLs.