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Genomics of Hematologic Cancers (Volume II)

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (30 November 2024) | Viewed by 740

Special Issue Editors


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Guest Editor
Chair and Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-081 Lublin, Poland
Interests: haematological neoplasms; multiple myeloma; mastocytosis; biomarkers; molecular biology; genetics; epigenetics; predictive factors; prognostic factors; targeted therapy
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-081 Lublin, Poland
Interests: haematological neoplasms; multiple myeloma; leukemia; lymphoma; mastocytosis; biomarkers; molecular biology; genetics; epigenetics; predictive factors; prognostic factors; targeted therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hematologic malignancies account for 10% of all cancers around the world and have become more frequent over the past years. Despite the huge progress associated with the improvements in hematologic molecular diagnostics and the development of targeted therapies such as kinase inhibitors, monoclonal antibodies, CART-cells, and bispecific antibodies, most hematologic cancers remain incurable diseases.

Applying genomic analysis based on high-throughput sequencing technologies has been rapidly expanding our understanding of cancer’s origin and complexity, providing us with more reliable information on its progression, metastases, and survival. Genome sequencing can provide information on the full spectrum of genetic mutations that trigger or contribute to cancer development and how cancer evolves in response to treatments.

In this way, cancer genome profiling is currently widely applied to routine clinical practice and has enabled the detection of predictive biomarkers of response for treatment.

This Special Issue is devoted to the application of genomics in identifying new cancer targets and developing new targeted therapies in hematologic cancers.

Dr. Aneta Szudy-Szczyrek
Prof. Dr. Marek Hus
Guest Editors

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Keywords

  • genomics
  • cancer
  • hematological malignancy
  • leukemia
  • lymphoma
  • myeloma
  • whole-genome sequencing
  • precision cancer medicine
  • target gene
  • targeted therapy
  • personalized medicine

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Published Papers (1 paper)

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Research

19 pages, 2482 KiB  
Article
Modeling the t(2;5) Translocation of Anaplastic Large Cell Lymphoma Using CRISPR-Mediated Chromosomal Engineering
by Robin Khan, Laurent Phely, Sophia Ehrenfeld, Tatjana Schmitz, Pia Veratti, Jakob Wolfes, Khalid Shoumariyeh, Geoffroy Andrieux, Uta S. Martens, Stephan de Bra, Martina Auer, Oliver Schilling, Melanie Boerries, Michael Speicher, Anna L. Illert, Justus Duyster and Cornelius Miething
Cancers 2025, 17(13), 2226; https://doi.org/10.3390/cancers17132226 - 2 Jul 2025
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Abstract
Background/Objectives: ALK+ Anaplastic Large Cell Lymphoma (ALCL) is an aggressive T-cell lymphoma that is characterized by expression of the Anaplastic Lymphoma Kinase (ALK), which is induced by the t(2;5) chromosomal rearrangement, leading to the expression of the NPM-ALK fusion oncogene. Most previous preclinical [...] Read more.
Background/Objectives: ALK+ Anaplastic Large Cell Lymphoma (ALCL) is an aggressive T-cell lymphoma that is characterized by expression of the Anaplastic Lymphoma Kinase (ALK), which is induced by the t(2;5) chromosomal rearrangement, leading to the expression of the NPM-ALK fusion oncogene. Most previous preclinical models of ALK+ ALCL were based on overexpression of the NPM-ALK cDNA from heterologous promoters. Due to the enforced expression, this approach is prone to artifacts arising from synthetic overexpression, promoter competition and insertional variation. Methods: To improve the existing ALCL models and more closely recapitulate the oncogenic events in ALK+ ALCL, we employed CRISPR/Cas-based chromosomal engineering to selectively introduce translocations between the Npm1 and Alk gene loci in murine cells. Results: By inducing precise DNA cleavage at the syntenic loci on chromosome 11 and 17 in a murine IL-3-dependent Ba/F3 reporter cell line, we generated de novo Npm-Alk translocations in vivo, leading to IL-3-independent cell growth. To verify efficient recombination, we analyzed the expression of the NPM-ALK fusion protein in the recombined cells and could also show the t(11;17) in the IL-3 independent Ba/F3 cells. Subsequent functional testing of these cells using an Alk-inhibitor showed exquisite responsiveness towards Crizotinib, demonstrating strong dependence on the newly generated ALK fusion oncoprotein. Furthermore, a comparison of the gene expression pattern between Ba/F3 cells overexpressing the Npm-Alk cDNA with Ba/F3 cells transformed by CRISPR-mediated Npm-Alk translocation indicated that, while broadly overlapping, a set of pathways including the unfolded protein response pathway was increased in the Npm-Alk overexpression model, suggesting increased reactive changes induced by exogenous overexpression of Npm-Alk. Furthermore, we observed clustered expression changes in genes located in chromosomal regions close to the breakpoint in the new CRISPR-based model, indicating positional effects on gene expression mediated by the translocation event, which are not part of the older models. Conclusions: Thus, CRISPR-mediated recombination provides a novel and more faithful approach to model oncogenic translocations, which may lead to an improved understanding of the molecular pathogenesis of ALCL and enable more accurate therapeutic models of malignancies driven by oncogenic fusion proteins. Full article
(This article belongs to the Special Issue Genomics of Hematologic Cancers (Volume II))
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