Advances in Molecular Pathogenesis and Targeted Therapies for Multiple Myeloma

Topic Information

Dear Colleagues,

We are delighted to announce a call for submissions to a Topic on the theme of “Advances in Molecular Pathogenesis and Targeted Therapies for Multiple Myeloma”.

Multiple myeloma (MM) is the second most common hematological malignancy globally, and despite enormous progress in its treatment armamentarium, MM remains incurable. Among the main limitations and barriers to cure are the heterogeneity of phase III studies and the absence of real-world data to address its considerable clinical and molecular heterogeneity, precluding its accurate prognostication and the development of optimal personalized treatment strategies. Current prognostication models (most commonly R-ISS) incorporate clinical and molecular features for risk stratification, with well-recognized knowledge gaps and technical limitations with current methodologies, and do not incorporate adverse non-genomic prognostic features including extramedullary disease and circulating tumor cells. To enable clinicians to select the optimal risk-adapted therapy for individual patients, there is a critical need to integrate all of the relevant clinical, biological, and molecular features, which can potentially be achieved with evolving technologies such as artificial intelligence (AI). Within this Topic, we outline recent advances in our understanding of the molecular pathogenesis of MM, focusing on the improvement of risk stratification and the integration of complex information and emerging targeted therapies to bring us closer to a future where personalized treatment for individual patients may become the new standard of care of patients with MM.

Topics may include but are not limited to the following:

• The application of genomics and proteomics in the understanding of MM pathogenesis and its resistance mechanisms, with the identification of novel therapeutic targets and biomarker-driven treatment strategies.
• The role of MM microbiome in identifying future biomarkers or therapeutic agents
• The use of bioinformatics and artificial intelligence including machine learning in the integration of big data, multi-omics, and the development of predictive models in the management of MM patients
• Precision medicine strategies for patients at high risk of progression, including early intervention and personalized therapeutic approaches
• Clinical implications of predicting survival and progression risk for patient management and outcomes, including risk-adapted treatment strategies and quality of life measures.

We encourage the submission of both original research articles and reviews. All submitted articles will be considered to undergo peer review.

Dr. Chung Hoow Kok
Dr. Cindy H. S. Lee
Dr. Claudio Cerchione
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomedicines biomedicines	3.9	6.8	2013	14.6 Days	CHF 2600	Submit
Biomolecules biomolecules	4.8	9.2	2011	18.4 Days	CHF 2700	Submit
Cancers cancers	4.5	8.8	2009	17.4 Days	CHF 2900	Submit
Cells cells	5.1	10.5	2012	17 Days	CHF 2700	Submit
Hematology Reports hematolrep	1.1	1.4	2009	39.1 Days	CHF 1600	Submit
International Journal of Molecular Sciences ijms	4.9	9.0	2000	16.8 Days	CHF 2900	Submit

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Published Papers (2 papers)

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All Biomedicines Biomolecules Cancers Cells Hematology Reports IJMS

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26 pages, 1575 KiB  

Open AccessReview

CXCR Family and Hematologic Malignancies in the Bone Marrow Microenvironment

by Yanquan Liu and Huanwen Tang

Biomolecules 2025, 15(5), 716; https://doi.org/10.3390/biom15050716 - 13 May 2025

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Abstract

Malignant hematologic diseases, also referred to as hematologic tumors, encompass a series of malignant proliferative disorders of the lymphopoietic system, including leukemia, lymphoma, multiple myeloma, and myeloproliferative neoplasms. The dysregulation of inflammatory factors or chronic inflammatory responses plays an indispensable role in the [...] Read more.

Malignant hematologic diseases, also referred to as hematologic tumors, encompass a series of malignant proliferative disorders of the lymphopoietic system, including leukemia, lymphoma, multiple myeloma, and myeloproliferative neoplasms. The dysregulation of inflammatory factors or chronic inflammatory responses plays an indispensable role in the onset and progression of these tumors. The C-X-C motif chemokine receptor (CXCR) serves as a key mediator of immune-inflammatory responses. Through its specific regulatory mechanisms, CXCR is involved in the transduction and activation of various signaling pathways, thereby mediating the malignant biological characteristics of blood tumor cells, such as uncontrolled proliferation, differentiation, invasion, migration, autophagy, and apoptosis. In the bone marrow microenvironment, CXCR plays a pivotal role. This review systematically analyzes and elucidates the roles and mechanisms of the CXCR family in hematologic malignancies, aiming to provide new insights into the biological mechanisms and clinical significance of these diseases. The CXCR family holds great potential as a molecular marker for both fundamental research and the clinical diagnosis and treatment of hematologic malignancies. Full article

(This article belongs to the Topic Advances in Molecular Pathogenesis and Targeted Therapies for Multiple Myeloma)

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18 pages, 2990 KiB  

Open AccessArticle

Prognostic Value of Post-Transplant MRD Negativity in Standard Versus High- and Ultra-High-Risk Multiple Myeloma Patients

by Lea Jasmin Kündgen, Dilara Akhoundova, Michele Hoffmann, Myriam Legros, Inna Shaforostova, Katja Seipel, Ulrike Bacher and Thomas Pabst

Cancers 2025, 17(9), 1565; https://doi.org/10.3390/cancers17091565 - 4 May 2025

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Abstract

Background: Cytogenetic abnormalities and the persistence of minimal residual disease (MRD) following autologous stem cell transplantation (ASCT) are two established prognostically unfavorable biomarkers in multiple myeloma (MM). Previous studies have shown that post-transplant MRD status is a powerful predictor of progression-free survival (PFS) [...] Read more.

Background: Cytogenetic abnormalities and the persistence of minimal residual disease (MRD) following autologous stem cell transplantation (ASCT) are two established prognostically unfavorable biomarkers in multiple myeloma (MM). Previous studies have shown that post-transplant MRD status is a powerful predictor of progression-free survival (PFS) and overall survival (OS). However, the impact of MRD remains poorly characterized in MM patients with high- or ultra-high-risk cytogenetics. Objectives: This study investigated the prognostic value of post-transplant MRD in standard- versus high- and ultra-high-risk MM. To this aim, we performed a retrospective analysis of 137 MM patients who underwent high-dose chemotherapy (HDCT) and ASCT at our institution between January 2019 and December 2021. Cytogenetics were assessed by fluorescence in situ hybridization. High-risk genomic alterations included del(17p), t(4;14), t(14;16), t(14;20), gain(1q), and TP53 mutations, with two or more alterations defining the ultra-high-risk category. MRD was assessed in bone marrow aspirates post-ASCT using flow cytometry. Results: Eighty-two (60%) patients were categorized as being at standard risk, forty (29%) as high risk, and fifteen (11%) as ultra-high risk. Median follow-up was 47 months. MRD negativity was achieved in 76 (55%) patients. At 48 months, the overall PFS rate was 61% (72%, 50%, and 32% for the standard-, high-, and ultra-high-risk subgroups, respectively; p = 0.0004), while the OS rate was 85% (89%, 79%, and 80% in standard-, high-, and ultra-high-risk MM patients, respectively; p = 0.1494). Within the standard-risk subgroup, longer PFS was observed for patients achieving MRD negativity (p = 0.0172). High- and ultra-high-risk patients showed no significant differences in PFS when stratified by MRD status, possibly due to prompt progression to MRD positivity. Conclusions: Our results suggest that high- and ultra-high-risk MM patients might benefit from closer response monitoring, including dynamic MRD assessment. Further, high- and ultra-high-risk patients might require a more intensive peri-transplant treatment. Full article

(This article belongs to the Topic Advances in Molecular Pathogenesis and Targeted Therapies for Multiple Myeloma)

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