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New Developments in Chronic Myeloid Leukemia

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 30 September 2025 | Viewed by 713

Special Issue Editor


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Guest Editor
1. Department of Oncology-Pathology, BioClinicum, Karolinska University Hospital, Solna, Stockholm, Sweden
2. Karolinska Institute, SE-17176 Stockholm, Sweden
Interests: cancer and oncology; hematology; immunology in the medical area

Special Issue Information

Dear Colleagues,

This Special Issue aims to highlight the latest advancements in the understanding and management of chronic myeloid leukemia (CML). Contributions will cover a wide spectrum of topics, ranging from the etiology and epidemiology of the disease to emerging strategies in diagnosis and treatment.

Key focus areas include the following:

  • Etiology and Epidemiology:
    Insights into the causes, risk factors, and global trends in CML incidence.
  • Diagnostic Advances:
    • Identification of novel molecular and clinical markers.
    • Improvements in early detection and prognostic evaluation.
    • Role of genetic alterations and chromosomal abnormalities in disease progression.
  • Therapeutic Innovations:
    • Development and optimization of small-molecule Tyrosine Kinase Inhibitors (TKIs) as first-line treatments.
    • Exploration of biological therapies such as allogeneic stem cell transplantation and Interferon-alpha.
    • Emerging strategies in chemotherapy and supportive care.
    • Results from clinical trials and therapies currently in the development pipeline.

This Special Issue welcomes original research articles, reviews, and short communications that contribute to the evolving landscape of CML research and clinical practice. We hope to provide a comprehensive overview of the most promising directions in the fight against CML.

Dr. Parviz Kokhaei
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • CML
  • small molecule inhibitors
  • biologicall treatment
  • prognostic markers

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Published Papers (1 paper)

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Research

19 pages, 8019 KiB  
Article
Identification of a PAK6-Mediated MDM2/p21 Axis That Modulates Survival and Cell Cycle Control of Drug-Resistant Stem/Progenitor Cells in Chronic Myeloid Leukemia
by Andrew Wu, Min Chen, Athena Phoa, Zesong Yang, Donna L. Forrest and Xiaoyan Jiang
Int. J. Mol. Sci. 2025, 26(13), 6533; https://doi.org/10.3390/ijms26136533 - 7 Jul 2025
Viewed by 578
Abstract
Chronic myeloid leukemia (CML) is a leading example of a malignancy where a molecular targeted therapy revolutionized treatment but has rarely led to cures. Overcoming tyrosine kinase inhibitor (TKI) drug resistance remains a challenge in the treatment of CML. We have recently identified [...] Read more.
Chronic myeloid leukemia (CML) is a leading example of a malignancy where a molecular targeted therapy revolutionized treatment but has rarely led to cures. Overcoming tyrosine kinase inhibitor (TKI) drug resistance remains a challenge in the treatment of CML. We have recently identified miR-185 as a predictive biomarker where reduced expression in CD34+ treatment-naïve CML cells was associated with TKI resistance. We have also identified PAK6 as a target gene of miR-185 that was upregulated in CD34+ TKI-nonresponder cells. However, its role in regulating TKI resistance remains largely unknown. In this study, we specifically targeted PAK6 in imatinib (IM)-resistant cells and CD34+ stem/progenitor cells from IM-nonresponders using a lentiviral-mediated PAK6 knockdown strategy. Interestingly, the genetic and pharmacological suppression of PAK6 significantly reduced proliferation and increased apoptosis in TKI-resistant cells. Cell survivability was further diminished when IM was combined with PAK6 knockdown. Importantly, PAK6 inhibition in TKI-resistant cells induced cell cycle arrest in the G2-M phase and cellular senescence, accompanied by increased levels of DNA damage-associated senescence markers. Mechanically, we identified a PAK6-mediated MDM2-p21 axis that regulates cell cycle arrest and senescence. Thus, PAK6 plays a critical role in determining alternative cell fates in leukemic cells, and targeting PAK6 may offer a therapeutic strategy to selectively eradicate TKI-resistant cells. Full article
(This article belongs to the Special Issue New Developments in Chronic Myeloid Leukemia)
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