About this Research Topic
Personalized treatment for solid tumors based on biomarkers has seen significant advancements in recent years. For chronic lymphocytic leukemia (CLL) and Waldenström macroglobulinemia (WM) identification of unique biomarkers is pending. For CLL certain biomarkers such as TP53 mutations, 17p deletion, and IGHV mutational status have been associated with prognosis and treatment response. Dysregulation of the B-cell receptor (BR) signaling pathway and several molecular targets including CD20, bruton's tyrosine kinase (BTK), CXCR4, CD32, and CD5 are involved in the pathogenesis of B-CLL. Alterations in genes involved in DNA damage response and repair, such as ATM and TP53, contribute to genomic instability and chemoresistance. Similarly, in Waldenström macroglobulinemia, somatic mutations in MYD88 and CXCR4 genes have been recognized as pivotal in disease pathogenesis and have implications for therapeutic targeting.
The aim of this topic is to identify actionable targets for personalized therapies in the second line treatment and future potential for personalized treatments in the first line according to predictive markers, MicroRNAs (miRNAs) and epigenetic alterations play crucial roles in the development and progression of CLL and WM. These regulatory mechanisms contribute to the dysregulation of gene expression, ultimately impacting the pathogenesis of these diseases. Numerous studies have identified specific miRNAs that are dysregulated and have been implicated in disease pathogenesis. For example, miR-15a and miR-16-1, which are located at the 13q14 chromosomal region frequently deleted in CLL, are downregulated and contribute to the overexpression of anti-apoptotic proteins such as BCL2. Conversely, miR-155 is upregulated in CLL and WM and has been associated with the activation of pro-survival pathways and the promotion of malignant B-cell proliferation. Furthermore, non-coding RNAs, such as long non-coding RNAs (IncRNAs) and circular RNAs (circRNAs) are also involved.
Epigenetic alterations, including DNA methylation, histone modifications, and non-coding RNA-associated gene silencing are also involved. In CLL global hypomethylation and specific hypermethylation of gene promoter regions have been observed, leading to the silencing of critical tumor suppressor genes e.g. CDKNA gene, which encodes the p16 protein involved in cell cycle regulation.
Also, the tumor microenvironment plays a pivotal role in these diseases. The interactions between malignant B cells and the surrounding stromal, immune, vascular components, chemokines, and extracellular matrix contribute to disease development and influence treatment responses. For instance, the SDF-1/CXCR4 axis is involved in the homing and retention of CLL and WM cells within the supportive niches of lymphoid tissues, bone-marrow, or spleen.
We welcome authors to contribute to our collection, and we invite original research articles, case reports, reviews, mini-reviews, opinion papers, and perspective articles that delve into the discovery of biomarkers and future directions of personalized therapy in CLL and WM. Specific themes of interest include the tumor microenvironment, immune evasion mechanisms, novel immunotherapeutic targets, and personalized immunotherapy approaches. We strongly encourage contributions that focus on potential intracellular molecular pathway interactions and microenvironment interactions that may contribute to the development of new combination treatment strategies.
The aim of this topic is to identify actionable targets for personalized therapies in the second line treatment and future potential for personalized treatments in the first line according to predictive markers, MicroRNAs (miRNAs) and epigenetic alterations play crucial roles in the development and progression of CLL and WM. These regulatory mechanisms contribute to the dysregulation of gene expression, ultimately impacting the pathogenesis of these diseases. Numerous studies have identified specific miRNAs that are dysregulated and have been implicated in disease pathogenesis. For example, miR-15a and miR-16-1, which are located at the 13q14 chromosomal region frequently deleted in CLL, are downregulated and contribute to the overexpression of anti-apoptotic proteins such as BCL2. Conversely, miR-155 is upregulated in CLL and WM and has been associated with the activation of pro-survival pathways and the promotion of malignant B-cell proliferation. Furthermore, non-coding RNAs, such as long non-coding RNAs (IncRNAs) and circular RNAs (circRNAs) are also involved.
Epigenetic alterations, including DNA methylation, histone modifications, and non-coding RNA-associated gene silencing are also involved. In CLL global hypomethylation and specific hypermethylation of gene promoter regions have been observed, leading to the silencing of critical tumor suppressor genes e.g. CDKNA gene, which encodes the p16 protein involved in cell cycle regulation.
Also, the tumor microenvironment plays a pivotal role in these diseases. The interactions between malignant B cells and the surrounding stromal, immune, vascular components, chemokines, and extracellular matrix contribute to disease development and influence treatment responses. For instance, the SDF-1/CXCR4 axis is involved in the homing and retention of CLL and WM cells within the supportive niches of lymphoid tissues, bone-marrow, or spleen.
We welcome authors to contribute to our collection, and we invite original research articles, case reports, reviews, mini-reviews, opinion papers, and perspective articles that delve into the discovery of biomarkers and future directions of personalized therapy in CLL and WM. Specific themes of interest include the tumor microenvironment, immune evasion mechanisms, novel immunotherapeutic targets, and personalized immunotherapy approaches. We strongly encourage contributions that focus on potential intracellular molecular pathway interactions and microenvironment interactions that may contribute to the development of new combination treatment strategies.
Keywords: molecular targets, personalised treatment, Waldenström macroglobulinemia, CD20, bruton tyrosine kinase, CXCR4
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