ijms-logo

Journal Browser

Journal Browser

Special Issue "Recent Advances of Leukemia Pathophysiology: From Molecular Basis to Targeted Therapies"

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

Deadline for manuscript submissions: 30 November 2021.

Special Issue Editor

Dr. Paulina Podszywałow-Bartnicka
E-Mail
Guest Editor
Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland
Interests: myeloid leukemia; therapy resistance; microenvironment; hypoxia; mRNA translation; RNA-binding proteins

Special Issue Information

Dear Colleagues,

This Special Issue will focus on molecular mechanisms supporting leukemia development, which could be used as targets for precision medicine.

The occurrence of an oncogene is a factor driving malignant transformation, which is followed by deep molecular changes. Variation in gene expression regulation has an impact on the course of cellular processes. Leukemia development is related to the progressive dysregulation of cell signaling due to the affected level of proteins playing a regulatory role in cellular pathways. The basis of this alteration is mostly a malfunction of factors controlling gene expression at the stage of transcription (e.g., DNA methylation, transcription factors) or post-transcriptionally (e.g., splicing, mRNA modification and turnover) through translation process (e.g., mRNA translation initiation or ribosome heterogeneity). Recent advances demonstrate that these factors contribute to cancer progression by an indirect influence on cellular processes essential for cancer cells’ propagation and survival of chemotherapy, such as cell quiescence/proliferation, differentiation, or apoptosis. Moreover, improper control of cell-cycle progression as well as DNA damage signaling and repair enhance genomic instability, pushing forward the progression of leukemia. 

The aim of this Special Issue is to highlight recently discovered molecular constituents emerging as potential therapeutic targets, which contribute to leukemia progression and chemo-resistance by affecting cellular signaling, gene expression, post-transcriptional regulation, or protein translation processes. Original papers and reviews are invited for submission.

Dr. Paulina Podszywałow-Bartnicka
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 papers will be 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

  • leukemia
  • regulation of gene expression
  • transcription
  • post-transcriptional regulation
  • translation
  • protein synthesis
  • proliferation
  • quiescence
  • apoptosis
  • differentiation
  • cell cycle
  • DNA damage and repair
  • precision medicine
  • therapy resistance
  • signaling

Published Papers (2 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Article
Genetic and Epigenetic Characterization of a Discordant KMT2A/AFF1-Rearranged Infant Monozygotic Twin Pair
Int. J. Mol. Sci. 2021, 22(18), 9740; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22189740 - 09 Sep 2021
Viewed by 377
Abstract
The KMT2A/AFF1 rearrangement is associated with an unfavorable prognosis in infant acute lymphocytic leukemia (ALL). Discordant ALL in monozygotic twins is uncommon and represents an attractive resource to evaluate intrauterine environment–genetic interplay in ALL. Mutational and epigenetic profiles were characterized for a discordant [...] Read more.
The KMT2A/AFF1 rearrangement is associated with an unfavorable prognosis in infant acute lymphocytic leukemia (ALL). Discordant ALL in monozygotic twins is uncommon and represents an attractive resource to evaluate intrauterine environment–genetic interplay in ALL. Mutational and epigenetic profiles were characterized for a discordant KMT2A/AFF1-rearranged infant monozygotic twin pair and their parents, and they were compared to three independent KMT2A/AFF1-positive ALL infants, in which the DNA methylation and gene expression profiles were investigated. A de novo Q61H NRAS mutation was detected in the affected twin at diagnosis and backtracked in both twins at birth. The KMT2A/AFF1 rearrangement was absent at birth in both twins. Genetic analyses conducted at birth gave more insights into the timing of the mutation hit. We identified correlations between DNA methylation and gene expression changes for 32 genes in the three independent affected versus remitted patients. The strongest correlations were observed for the RAB32, PDK4, CXCL3, RANBP17, and MACROD2 genes. This epigenetic signature could be a putative target for the development of novel epigenetic-based therapies and could help in explaining the molecular mechanisms characterizing ALL infants with KMT2A/AFF1 fusions. Full article
Show Figures

Figure 1

Review

Jump to: Research

Review
Therapeutic Targeting of the Leukaemia Microenvironment
Int. J. Mol. Sci. 2021, 22(13), 6888; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22136888 - 26 Jun 2021
Cited by 1 | Viewed by 957
Abstract
In recent decades, the conduct of uniform prospective clinical trials has led to improved remission rates and survival for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia. However, high-risk patients continue to have inferior outcomes, where chemoresistance and relapse are common due [...] Read more.
In recent decades, the conduct of uniform prospective clinical trials has led to improved remission rates and survival for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia. However, high-risk patients continue to have inferior outcomes, where chemoresistance and relapse are common due to the survival mechanisms utilised by leukaemic cells. One such mechanism is through hijacking of the bone marrow microenvironment, where healthy haematopoietic machinery is transformed or remodelled into a hiding ground or “sanctuary” where leukaemic cells can escape chemotherapy-induced cytotoxicity. The bone marrow microenvironment, which consists of endosteal and vascular niches, can support leukaemogenesis through intercellular “crosstalk” with niche cells, including mesenchymal stem cells, endothelial cells, osteoblasts, and osteoclasts. Here, we summarise the regulatory mechanisms associated with leukaemia–bone marrow niche interaction and provide a comprehensive review of the key therapeutics that target CXCL12/CXCR4, Notch, Wnt/b-catenin, and hypoxia-related signalling pathways within the leukaemic niches and agents involved in remodelling of niche bone and vasculature. From a therapeutic perspective, targeting these cellular interactions is an exciting novel strategy for enhancing treatment efficacy, and further clinical application has significant potential to improve the outcome of patients with leukaemia. Full article
Show Figures

Figure 1

Back to TopTop