Abstract
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 terminates into a blast crisis (BC). BC transformation is associated with accumulation of CD34+ blasts. We investigated the expression and phosphorylation of Src-homology-2 and collagen-homology domains (Shc) proteins in subpopulations of CML primary cells. Shc polypeptides are tyrosine kinase substrates that are constitutively tyrosine-phosphorylated in continuous cell lines 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- fractions from CML-CP and normal bone marrow expressed low levels of p46(Shc). Shc proteins were constitutively phosphorylated in the CD34+ fractions from 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 leukemogenesis: (a) dramatic changes of Shc expression during terminal differentiation of hemopoietic cells adds a further level of regulation to the signal transduction function of Shc; and (b) constitutive Shc tyrosine- phosphorylation in the rare CD34+ cells of CML-CP might contribute to the selection of this subpopulation during the blast crisis transformation of CMLs.
| Original language | English |
|---|---|
| Pages (from-to) | 728-732 |
| Number of pages | 5 |
| Journal | Cancer Research |
| Volume | 60 |
| Issue number | 3 |
| Publication status | Published - Feb 1 2000 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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Selective expression and constitutive phosphorylation of Src-homology-2 and collagen-homology domains proteins in the CD34+ fraction of chronic myelogenous leukemias. / Bonati, Antonio; Carlo-Stella, Carmelo; Lunghi, Paolo; Albertini, Roberto; Pinelli, Silvana; Migliaccio, Enrica; Sammarelli, Gabriella; Savoldo, Barbara; Tabilio, Antonio; Dall'Aglio, Pier Paolo; Pelicci, Pier Giuseppe.
In: Cancer Research, Vol. 60, No. 3, 01.02.2000, p. 728-732.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Selective expression and constitutive phosphorylation of Src-homology-2 and collagen-homology domains proteins in the CD34+ fraction of chronic myelogenous leukemias
AU - Bonati, Antonio
AU - Carlo-Stella, Carmelo
AU - Lunghi, Paolo
AU - Albertini, Roberto
AU - Pinelli, Silvana
AU - Migliaccio, Enrica
AU - Sammarelli, Gabriella
AU - Savoldo, Barbara
AU - Tabilio, Antonio
AU - Dall'Aglio, Pier Paolo
AU - Pelicci, Pier Giuseppe
PY - 2000/2/1
Y1 - 2000/2/1
N2 - 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 terminates into a blast crisis (BC). BC transformation is associated with accumulation of CD34+ blasts. We investigated the expression and phosphorylation of Src-homology-2 and collagen-homology domains (Shc) proteins in subpopulations of CML primary cells. Shc polypeptides are tyrosine kinase substrates that are constitutively tyrosine-phosphorylated in continuous cell lines 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- fractions from CML-CP and normal bone marrow expressed low levels of p46(Shc). Shc proteins were constitutively phosphorylated in the CD34+ fractions from 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 leukemogenesis: (a) dramatic changes of Shc expression during terminal differentiation of hemopoietic cells adds a further level of regulation to the signal transduction function of Shc; and (b) constitutive Shc tyrosine- phosphorylation in the rare CD34+ cells of CML-CP might contribute to the selection of this subpopulation during the blast crisis transformation of CMLs.
AB - 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 terminates into a blast crisis (BC). BC transformation is associated with accumulation of CD34+ blasts. We investigated the expression and phosphorylation of Src-homology-2 and collagen-homology domains (Shc) proteins in subpopulations of CML primary cells. Shc polypeptides are tyrosine kinase substrates that are constitutively tyrosine-phosphorylated in continuous cell lines 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- fractions from CML-CP and normal bone marrow expressed low levels of p46(Shc). Shc proteins were constitutively phosphorylated in the CD34+ fractions from 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 leukemogenesis: (a) dramatic changes of Shc expression during terminal differentiation of hemopoietic cells adds a further level of regulation to the signal transduction function of Shc; and (b) constitutive Shc tyrosine- phosphorylation in the rare CD34+ cells of CML-CP might contribute to the selection of this subpopulation during the blast crisis transformation of CMLs.
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M3 - Article
C2 - 10676660
AN - SCOPUS:0033950896
VL - 60
SP - 728
EP - 732
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 3
ER -