Kinase-Dependent Crosstalk Between CLL Cells and the Tumor Microenvironment

Dear Colleagues,

Chronic lymphocytic leukemia (CLL) is characterized by profound alterations in intracellular signaling networks tightly orchestrated by kinases and phosphatases. These enzymes play crucial roles in regulating B-cell receptor (BCR) signaling, survival pathways, cytoskeletal dynamics, DNA damage responses, and interactions with stromal and immune cell subsets. In recent years, it has become clear that CLL progression is not solely determined by intrinsic genetic lesions but is also strongly driven by reciprocal interactions between leukemic cells and the tumor microenvironment (TME).

Kinase-dependent pathways, including those involving BTK, PI3K, SYK, AKT, MAPKs, JAK/STAT, AURKA/AURKB, and CK2, mediate key aspects of this bidirectional communication, influencing CLL cell survival, proliferation, immune evasion, metabolic adaptation, and resistance to therapy. Likewise, microenvironmental signals arising from nurse-like cells, mesenchymal stromal cells, T cells, macrophages, and extracellular vesicles converge on kinase hubs that shape disease behavior.

This Special Issue highlights recent advances in our understanding of kinase-dependent crosstalk between CLL cells and TME. We welcome contributions that investigate how kinase and phosphatase signaling networks integrate extracellular cues, modulate leukemic cell fate, and provide opportunities for targeted therapeutic intervention. Submissions may include molecular studies, preclinical models, translational investigations, clinical correlations, and emerging therapeutic strategies.

Topics of interest:

• Kinase-driven signaling pathways regulating CLL–TME interactions;
• Phosphatases and their regulatory role in leukemic cell communication;
• BTK, PI3K, SYK, and downstream effectors in stromal-mediated survival;
• Kinase involvement in immune evasion and T-cell dysfunction in CLL;
• Interplay between microenvironmental cytokines/chemokines and kinase activation;
• Kinase-mediated remodeling of metabolism, migration, and adhesion;
• Drug resistance mechanisms linked to kinase or phosphatase deregulation;
• In vitro and in vivo models dissecting CLL–TME interactions;
• Multi-omics approaches to decode kinase signaling dynamics;
• Novel kinase inhibitors or combination therapies targeting TME-dependent pathways.

We encourage submissions from basic, translational, and clinical research groups.

Dr. Fábio Oliveira
Prof. Dr. Nicola Perrotti
Guest Editors

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 250 words) can be sent to the Editorial Office for assessment.

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. Kinases and Phosphatases is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• chronic lymphocytic leukemia
• kinase signaling
• tumor microenvironment