Selective expression and constitutive phosphorylation of Src-homology-2 and collagen-homology domains proteins in the CD34+ fraction of chronic myelogenous leukemias

Antonio Bonati, Carmelo Carlo-Stella, Paolo Lunghi, Roberto Albertini, Silvana Pinelli, Enrica Migliaccio, Gabriella Sammarelli, Barbara Savoldo, Antonio Tabilio, Pier Paolo Dall'Aglio, Pier Giuseppe Pelicci

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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 languageEnglish
Pages (from-to)728-732
Number of pages5
JournalCancer Research
Volume60
Issue number3
Publication statusPublished - Feb 1 2000

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Blast Crisis
Collagen
Phosphorylation
Leukemia, Myeloid, Chronic Phase
Lymphocyte Activation
Protein-Tyrosine Kinases
Tyrosine
Bone Marrow
Protein Domains
Cell Differentiation
Signal Transduction
Proteins
Cell Line
Peptides

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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 journalArticle

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. / Selective expression and constitutive phosphorylation of Src-homology-2 and collagen-homology domains proteins in the CD34+ fraction of chronic myelogenous leukemias. In: Cancer Research. 2000 ; Vol. 60, No. 3. pp. 728-732.
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AU - Albertini, Roberto

AU - Pinelli, Silvana

AU - Migliaccio, Enrica

AU - Sammarelli, Gabriella

AU - Savoldo, Barbara

AU - Tabilio, Antonio

AU - Dall'Aglio, Pier Paolo

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