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Inverse regulation of bridging integrator 1 and BCR-ABL1 in chronic myeloid leukemia

Stefania Trino1, Luciana De Luca2, Vittorio Simeon2

  • 1Laboratory of Pre-clinical and Translational Research, IRCCS Referral Cancer Center of Basilicata, Rionero in Vulture, PZ, Italy. stefania.trino@crob.it.

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
|July 22, 2015
PubMed

Insights

Bridging integrator 1 (BIN1) and Rab interactor 1 (RIN1) are downregulated in chronic myeloid leukemia (CML), impacting tyrosine kinase receptor (RTK) endocytosis. Treatment restored BIN1 and RIN1 expression, suggesting a novel therapeutic target for CML.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Hematology

Background:

  • Endocytosis regulates tyrosine kinase receptor (RTK) activity.
  • Bridging integrator 1 (BIN1) is crucial for RTK intracellular trafficking.
  • Dysregulated RTK signaling is implicated in hematological malignancies.

Purpose of the Study:

  • To investigate the role of BIN1 and its activator Rab interactor 1 (RIN1) in chronic myeloid leukemia (CML).
  • To explore the impact of these proteins on RTK endocytosis in CML.
  • To assess the effect of tyrosine kinase inhibitors (TKIs) on BIN1 and RIN1 expression in CML.

Main Methods:

  • Studied gene expression in 34 CML patients at diagnosis and 57 patients undergoing TKI treatment.
  • Performed in vitro experiments on CML and non-tumorigenic cell lines treated with Imatinib.
  • Analyzed the correlation between BIN1-RIN1 and BCR-ABL1 expression.
  • Investigated AXL receptor internalization in K562 cells.

Main Results:

  • BIN1 and RIN1 were downregulated in CML patients compared to healthy controls.
  • TKI treatment, alongside BCR-ABL1 inactivation, increased BIN1 and RIN1 expression.
  • A significant inverse correlation was observed between BIN1-RIN1 and BCR-ABL1 expression.
  • Imatinib treatment induced BIN1-RIN1 upregulation and AXL receptor internalization in K562 cells.

Conclusions:

  • BIN1 and RIN1 play a role in the altered endocytosis of RTKs in CML.
  • Restoration of BIN1 and RIN1 expression by TKIs may help normalize RTK signaling.
  • BIN1 and RIN1 represent potential therapeutic targets for managing CML by modulating RTK endocytosis.

Keywords:
AXLBCR-ABL1Bridging integrator 1Chronic myeloid leukemiaRab interactor 1

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