International Journal of Molecular Sciences

Journal Browser

► Journal Browser

Special Issue Editors

Special Issue Information

Dear Colleagues,

Multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) are becoming the most prevalent hematological malignancies due to the incredible results achieved by the introduction of target therapy and immunotherapy. Unfortunately, these diseases unavoidably relapse and become incurable in the majority of patients. From a biological point of view, genomic alterations are already present in cancer cells from MM and CLL at their asymptomatic phase (i.e. when patients do not need treatment), supporting the idea that extrinsic mechanisms are needed to foster cancer progression. Indeed, both diseases are considered microenvironment-dependent malignancies, where cancer cells (aberrant plasma cells or mature B cells) co-operate with a supportive tissue microenvironment to generate chronic inflammation and severe immune effectors impairment.

To this end, this Special Issue “Recent Advances in Tumor Microenvironment and Molecular Targeting in Multiple Myeloma and Chronic Lymphocytic Leukemia” of the International Journal of Molecular Sciences focus on the biological, translational and clinical advances achieved by the targeting of tumor microenvironment and of actionable genomic lesions as well as on the mechanisms at the basis of treatment resistance, thus paving the way for the design of better treatment strategies.

We welcome original basic, translational and molecular biology-driven clinical research articles as well as review articles leading to improvement of the understanding of both MM and CLL pathogenesis.

Dr. Cirino Botta
Dr. Massimo Gentile
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 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.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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.

Keywords

multiple myeloma
chronic lymphocytic leukemia
smoldering myeloma
monoclonal antibodies
BTK inhibitors
BCL2 inhibitors
proteasome inhibitos
immunomodulatory drugs
chemotherapy
bone marrow microenvironment
T cell response
immunoregulatory cells

Published Papers (2 papers)

Download All Papers

Research

20 pages, 2830 KiB

Open AccessArticle

Identification of the Axis β-Catenin–BTK in the Dynamic Adhesion of Chronic Lymphocytic Leukemia Cells to Their Microenvironment

by Imane Mihoub, Tareck Rharass, Souhaïl Ouriemmi, Antonin Oudar, Laure Aubard, Valérie Gratio, Gregory Lazarian, Jordan Ferreira, Elisabetta Dondi, Florence Cymbalista, Vincent Levy, Fanny Baran-Marszak, Nadine Varin-Blank, Dominique Ledoux, Christine Le Roy and Laura Gardano

Int. J. Mol. Sci. 2023, 24(24), 17623; https://doi.org/10.3390/ijms242417623 - 18 Dec 2023

Viewed by 804

Abstract

In the microenvironment, cell interactions are established between different cell types to regulate their migration, survival and activation. β-Catenin is a multifunctional protein that stabilizes cell–cell interactions and regulates cell survival through its transcriptional activity. We used chronic lymphocytic leukemia (CLL) cells as a cellular model to study the role of β-catenin in regulating the adhesion of tumor cells to their microenvironment, which is necessary for tumor cell survival and accumulation. When co-cultured with a stromal cell line (HS-5), a fraction of the CLL cells adhere to stromal cells in a dynamic fashion regulated by the different levels of β-catenin expression. In non-adherent cells, β-catenin is stabilized in the cytosol and translocates into the nucleus, increasing the expression of cyclin D1. In adherent cells, the level of cytosolic β-catenin is low but membrane β-catenin helps to stabilize the adhesion of CLL to stromal cells. Indeed, the overexpression of β-catenin enhances the interaction of CLL with HS-5 cells, suggesting that this protein behaves as a regulator of cell adhesion to the stromal component and of the transcriptional regulation of cell survival. Inhibitors that block the stabilization of β-catenin alter this equilibrium and effectively disrupt the support that CLL cells receive from the cross-talk with the stroma. Full article

(This article belongs to the Special Issue Recent Advances in Tumor Microenvironment and Molecular Targeting in Multiple Myeloma and Chronic Lymphocytic Leukemia)

► Show Figures

Figure 1

13 pages, 2246 KiB

Open AccessArticle

Molecular-Biology-Driven Frontline Treatment for Chronic Lymphocytic Leukemia: A Network Meta-Analysis of Randomized Clinical Trials

by Andrea Rizzuto, Angelo Pirrera, Emilia Gigliotta, Salvatrice Mancuso, Candida Vullo, Giulia Maria Camarda, Cristina Rotolo, Arianna Roppolo, Corinne Spoto, Massimo Gentile, Cirino Botta and Sergio Siragusa

Int. J. Mol. Sci. 2023, 24(12), 9930; https://doi.org/10.3390/ijms24129930 - 9 Jun 2023

Cited by 2 | Viewed by 2180

Abstract

The treatment of chronic lymphocytic leukemia (CLL) currently relies on the use of chemo-immunotherapy, Bruton’s tyrosine kinase inhibitors, or BCL2 inhibitors alone or combined with an anti-CD20 monoclonal antibody. However, the availability of multiple choices for the first-line setting and a lack of direct head-to-head comparisons pose a challenge for treatment selection. To overcome these limitations, we performed a systematic review and a network meta-analysis on published randomized clinical trials performed in the first-line treatment setting of CLL. For each study, we retrieved data on progression-free survival (according to del17/P53 and IGHV status), overall response rate, complete response, and incidence of most frequent grade 3–4 adverse event. We identified nine clinical trials encompassing 11 different treatments, with a total of 5288 CLL patients evaluated. We systematically performed separated network meta-analyses (NMA) to evaluate the efficacy/safety of each regimen in the conditions previously described to obtain the surface under the cumulative ranking curve (SUCRA) score, which was subsequently used to build separated ranking charts. Interestingly, the combination of obinutuzumab with acalabrutinib reached the top of the chart in each sub-analysis performed, with the exception of the del17/P53mut setting, where it was almost on par with the aCD20 mAbs/ibrutinib combination (SUCRA aCD20-ibrutinib and O-acala: 93.5% and 91%, respectively) and of the safety evaluation, where monotherapies (acalabrutinib in particular) gave better results. Finally, considering that NMA and SUCRA work for single endpoints only, we performed a principal component analysis to recapitulate in a cartesian plane the SUCRA profiles of each schedule according to the results obtained in each sub-analysis, confirming again the superiority of aCD20/BTKi or BCL2i combinations in a first-line setting. Overall, here we demonstrated that: (1) a chemotherapy-free regimen, such as the combination of aCD20 with a BTKi or BCL2i, should be the preferred treatment choice despite biological/molecular characteristics (preferred regimen O-acala); (2) there is less and less room for chemotherapy in the first line treatment of CLL. Full article

(This article belongs to the Special Issue Recent Advances in Tumor Microenvironment and Molecular Targeting in Multiple Myeloma and Chronic Lymphocytic Leukemia)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Recent Advances in Tumor Microenvironment and Molecular Targeting in Multiple Myeloma and Chronic Lymphocytic Leukemia

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (2 papers)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI