Complementary functions of the antiapoptotic protein A1 and serine/threonine kinase pim-1 in the BCR/ABL-mediated leukemogenesis.

@article{NieborowskaSkorska2002ComplementaryFO,
  title={Complementary functions of the antiapoptotic protein A1 and serine/threonine kinase pim-1 in the BCR/ABL-mediated leukemogenesis.},
  author={Malgorzata Nieborowska-Skorska and Grażyna Hoser and Plamen M Kossev and Mariusz A Wasik and Tomasz Skorski},
  journal={Blood},
  year={2002},
  volume={99 12},
  pages={
          4531-9
        }
}
BCR/ABL oncogenic tyrosine kinase activates STAT5, which plays an important role in leukemogenesis. The downstream effectors of the BCR/ABL-->STAT5 pathway remain poorly defined. We show here that expression of the antiapoptotic protein A1, a member of the Bcl-2 family, and the serine/threonine kinase pim-1 are enhanced by BCR/ABL. This up-regulation requires activation of STAT5 by the signaling from SH3+SH2 domains of BCR/ABL. Enhanced expression of A1 and pim-1 played a key role in the BCR… 
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TLDR
It is suggested that PIMs are alternative therapeutic targets in PTK-mediated leukemia and that targeting the PIM kinase family could provide a new avenue to overcome resistance against small-molecule tyrosine kinase inhibitors.
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Pim-1 kinase inhibits STAT5-dependent transcription via its interactions with SOCS1 and SOCS3.
TLDR
It is demonstrated that Pim-1 inhibits STAT5-dependent transcription in cells responsive to interleukin-3, prolactin, or erythropoietin, and both Pim and SOCS family proteins may be components of a negative feedback mechanism that allows STAT5 to attenuate its own activity.
Pim-1 is up-regulated by constitutively activated FLT3 and plays a role in FLT3-mediated cell survival.
TLDR
It is demonstrated that constitutively activated FLT3 signaling up-regulates Pim-1 expression in leukemia cells, which contributes to the proliferative and antiapoptotic pathways induced by FLT 3 signaling.
with SOCS1 and SOCS3 Pim-1 kinase inhibits STAT5-dependent transcription via its interactions
TLDR
It is demonstrated that Pim-1 inhibits STAT5-dependent transcription in cells responsive to interleukin-3, prolactin or erythropoietin, and both Pim and SOCS family proteins may be components of a negative feedback mechanism that allows STAT5 to attenuate its own activity.
Role of c-Jun NH-terminal Kinase in Bcr/Abl Induced Cell Transformation: a dissertation
TLDR
The aim of this thesis is to examine the role of JNK in malignant transformation by using the Bcr/Abl oncogene as a transforming agent and dominant negative approaches demonstrate that inhibition of c-Jun or JNK prevents BCr/ Ablinduced cell transformation in vitro.
Identification of heme oxygenase-1 as a novel BCR/ABL-dependent survival factor in chronic myeloid leukemia.
TLDR
Overexpression of HO-1 in the CML-derived cell line K562 was found to counteract STI571-induced apoptosis and identifyHO-1 as a novel BCR/ABL-driven survival molecule and potential target in leukemic cells in patients with CML.
v-Abl signaling disrupts SOCS-1 function in transformed pre-B cells.
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