Nuclear-cytoplasmic Shuttling in Chronic Myeloid Leukemia: Implications in Leukemia Maintenance and Therapy

Carrà, Giovanna; Russo, Isabella; Guerrasio, Angelo; Morotti, Alessandro

doi:10.3390/cells8101248

Cited by 5 publications

(2 citation statements)

References 67 publications

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“…Physiological ABL in the nucleus inhibits cell growth, a function that is abolished once it is fused with BCR. However, inactivated BCR::ABL can enter the nucleus and, once entrapped there, it results in the apoptosis of all fusion-positive cells [161,162]. The kinase domain's overactivation and the phosphorylation of BCR aberrantly activates the MAPK, JAK/STAT, and PI3K/AKT pathways, enabling the cell to evade apoptosis while promoting proliferation [163].…”

Section: Bcr::ablmentioning

confidence: 99%

Decoding Oncofusions: Unveiling Mechanisms, Clinical Impact, and Prospects for Personalized Cancer Therapies

Salokas

Dashi

Varjosalo

2023

Cancers

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Cancer-associated gene fusions, also known as oncofusions, have emerged as influential drivers of oncogenesis across a diverse range of cancer types. These genetic events occur via chromosomal translocations, deletions, and inversions, leading to the fusion of previously separate genes. Due to the drastic nature of these mutations, they often result in profound alterations of cellular behavior. The identification of oncofusions has revolutionized cancer research, with advancements in sequencing technologies facilitating the discovery of novel fusion events at an accelerated pace. Oncofusions exert their effects through the manipulation of critical cellular signaling pathways that regulate processes such as proliferation, differentiation, and survival. Extensive investigations have been conducted to understand the roles of oncofusions in solid tumors, leukemias, and lymphomas. Large-scale initiatives, including the Cancer Genome Atlas, have played a pivotal role in unraveling the landscape of oncofusions by characterizing a vast number of cancer samples across different tumor types. While validating the functional relevance of oncofusions remains a challenge, even non-driver mutations can hold significance in cancer treatment. Oncofusions have demonstrated potential value in the context of immunotherapy through the production of neoantigens. Their clinical importance has been observed in both treatment and diagnostic settings, with specific fusion events serving as therapeutic targets or diagnostic markers. However, despite the progress made, there is still considerable untapped potential within the field of oncofusions. Further research and validation efforts are necessary to understand their effects on a functional basis and to exploit the new targeted treatment avenues offered by oncofusions. Through further functional and clinical studies, oncofusions will enable the advancement of precision medicine and the drive towards more effective and specific treatments for cancer patients.

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Section: Bcr::ablmentioning

confidence: 99%

Decoding Oncofusions: Unveiling Mechanisms, Clinical Impact, and Prospects for Personalized Cancer Therapies

Salokas

Dashi

Varjosalo

2023

Cancers

View full text Add to dashboard Cite

show abstract

“…However, the expression of the BCR/ABL oncogene prevents the UPS-mediated destruction of hnRNP A1 and enhances its ability to export mRNAs from the nucleus, possibly via PKCζ-dependent phosphorylation of this RBP. Increased cellular concentrations of hnRNP A1 and altered nucleocytoplasmic traffiking of its target transcripts have been related to BCR/ABL-mediated leukemogenesis (Iervolino et al, 2002;Carrà et al, 2019).…”

Section: Cancermentioning

confidence: 99%