Identification of CRKL as the constitutively phosphorylated 39-kD tyrosine phosphoprotein in chronic myelogenous leukemia cells.

@article{Nichols1994IdentificationOC,
  title={Identification of CRKL as the constitutively phosphorylated 39-kD tyrosine phosphoprotein in chronic myelogenous leukemia cells.},
  author={G L Nichols and Maribeth A. Raines and Juan Carlos Vera and Lynne Lacomis and Paul Tempst and David W. Golde},
  journal={Blood},
  year={1994},
  volume={84 9},
  pages={
          2912-8
        }
}
Chronic myelogenous leukemia (CML) is characterized by the presence of the Philadelphia (Ph) chromosome in clonally derived hematopoietic precursors and their progeny. The Ph chromosome arises from a translocation that deregulates the c-ABL protein tyrosine kinase, giving it transforming potential and increased kinase activity. We observed a unique 39-kD tyrosine phosphoprotein (pp39), previously reported in blastic CML cell lines, in neutrophils from 50 cases of chronic phase CML. This protein… 

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Crkl is constitutively tyrosine phosphorylated in platelets from chronic myelogenous leukemia patients and inducibly phosphorylated in normal platelets stimulated by thrombopoietin
TLDR
The pattern of protein tyrosine phosphorylation in platelets from 15 CML patients was examined and it was found that crkl is an endogenous substrate for calpain, a protease that may be involved in postaggregation signaling processes and that crk1 may have a role in signaling by thrombopoietin.
Crkl is constitutively tyrosine phosphorylated in platelets from chronic myelogenous leukemia patients and inducibly phosphorylated in normal platelets stimulated by thrombopoietin.
TLDR
The pattern of protein tyrosine phosphorylation in platelets from 15 CML patients was examined and it was found that crkl is an endogenous substrate for calpain, a protease that may be involved in postaggregation signaling processes and that crk1 may have a role in signaling by thrombopoietin.
Crkl Is Complexed with Tyrosine-phosphorylated Cbl in Ph-positive Leukemia (*)
TLDR
It is demonstrated here that this protein is Cbl, originally discovered as an oncogene which induces B-cell and myeloid leukemias in mice, and the existence of a trimolecular complex involving Bcr/Abl, Crkl, and Cbl is suggested, consistent with a model in which Crkl mediates the oncogenic signal of B Crkl to Cbl.
CRKL Links p210BCR/ABL with Paxillin in Chronic Myelogenous Leukemia Cells (*)
TLDR
Results suggest that the p210BCR/ABL oncogene may be physically linked to the focal adhesion-associated protein paxillin in hematopoietic cells by CRKL, which could contribute to the known adhesive defects of CML cells.
A specific need for CRKL in p210BCR-ABL-induced transformation of mouse hematopoietic progenitors.
TLDR
It is shown that CRKL is required for p210(BCR-ABL) to support interleukin-3-independent growth of myeloid progenitor cells and long-term outgrowth of B-lymphoid cells from fetal liver-derived hematopoietic progenitors cells.
BCR‐ABL oncoprotein is expressed by platelets from CML patients and associated with a special pattern of CrkL phosphorylation
TLDR
The presence of BCR‐ABL provides an explanation for the constitutive tyrosine phosphorylation of CrkL in CML platelets as no correlation was observed between platelet counts and platelet BCR-ABL protein expression, thrombocytosis or thromBocythaemia in C ML cannot be explained.
Second-generation tyrosine kinase inhibitors as therapy for chronic myeloid leukemia
TLDR
This review focuses on the relevant biology of CML, imatinib mesylate resistance mechanisms, and the current status of the next generation of Bcr-Abl inhibitors.
THE ROLE OF SRC FAMILY TYROSINE KINASES IN BCR-ABL SIGNAL TRANSDUCTION AND CHRONIC MYELOGENOUS LEUKEMIA
TLDR
An important role is established for Src family tyrosine kinases in Bcr-Abl-mediated oncogenic signaling and Src kinases are implicate as a promising therapeutic target for chronic myelogenous leukemia.
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