PTBP2 exon 10 inclusion is associated with the progression of CML and it is BCR-ABL1 dependent

Area of Science:

• Molecular Biology
• Oncology
• Cancer Research

Background:

• Aberrant splicing factor expression drives cancer progression.
• Polypyrimidine tract binding protein 2 (PTBP2) is known for its role in neuronal cells.
• The function of PTBP2 in chronic myeloid leukemia (CML) remains largely unexplored.

Purpose of the Study:

• To investigate the role of PTBP2 in chronic myeloid leukemia (CML).
• To explore the association between PTBP2 expression, alternative splicing, and CML progression.
• To evaluate PTBP2 as a potential therapeutic target in CML.

Main Methods:

• Comparative analysis of RNA binding protein (RBP) expression in CML blast crisis (CML-BC) and relapsed cases.
• Assessment of PTBP2 exon 10 inclusion in various CML cell lines and patient samples.
• Investigation of BCR-ABL1's effect on PTBP2 expression and splicing, and the impact of imatinib inhibition.
• Functional studies involving PTBP2 knockdown in KCL22 cells to assess proliferation, cell cycle, and apoptosis.

Main Results:

• Increased expression of PTBP2 and MSI2 was observed in CML-BC and relapsed CML cases.
• PTBP2 exon 10 inclusion was elevated in a granulocytic CML cell line (KCL22) and correlated with PTBP2 protein levels.
• BCR-ABL1 expression potentiates PTBP2 exon 10 inclusion; imatinib treatment inhibits this inclusion and affects PTBP2 expression.
• PTBP2 knockdown in KCL22 cells reduced proliferation, induced G2/M cell cycle arrest, and increased apoptosis.

Conclusions:

• PTBP2 is a potential novel therapeutic target for chronic myeloid leukemia (CML).
• The alternative splicing of PTBP2 exon 10, regulated by BCR-ABL1, plays a significant role in CML progression.
• Targeting PTBP2 or its splicing could offer a new strategy for CML treatment.