Hematopoietic Cell Lines as Models for Leukemia and Lymphoma

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 30 June 2026 | Viewed by 1115

Special Issue Editor


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Guest Editor
Department of Human and Animal Cell Lines, Leibniz-Institute DSMZ, 38124 Braunschweig, Germany
Interests: hematopoiesis; leukemia; lymphoma; transcription factor; homeobox genes

Special Issue Information

Dear Colleagues,

Hematopoietic malignancies share the same tissue of origin but manifest as diverse entities, types, and subtypes. Hematopoietic cell lines are derived from patients with specific types of leukemia and lymphoma and bear the chromosomal, genomic, genetic, and functional characteristics of the original tumor. Accordingly, these cell lines represent faithful models to investigate carcinogenesis and treatment approaches in vitro. However, it is essential that they are authenticated and carefully characterized for their benefits as experimental models to be extracted correctly. While some leukemia/lymphoma types and subtypes are well covered by such models, other entities lack corresponding cell lines and deserve redoubled effort to close these gaps.

This Special Issue seeks studies that describe novel hematopoietic cell lines or have used established cell lines for basic research as well as translational approaches, demonstrating their applications, advantages, and limitations.

Dr. Stefan Nagel
Guest Editor

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Keywords

  • hematopoiesis
  • leukemia
  • lymphoma
  • transcription factor
  • homeobox genes

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Published Papers (2 papers)

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Research

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17 pages, 3356 KB  
Article
Glycolytic Enzymes Are Part of an Oncogenic Network in AML
by Stefan Nagel, Corinna Meyer and Claudia Pommerenke
Cells 2026, 15(6), 569; https://doi.org/10.3390/cells15060569 - 23 Mar 2026
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Abstract
Erythroid acute myeloid leukemia (AML) cell line OCI-M2 expresses a particular oncogenic network: IRF6, in concert with ETV2 and HEY1, aberrantly activates NKL homeobox gene NKX2-4, which in turn represses megakaryocytic lineage factor FLI1. Interestingly, in keratinocytes, IRF6 is able to bind glucose [...] Read more.
Erythroid acute myeloid leukemia (AML) cell line OCI-M2 expresses a particular oncogenic network: IRF6, in concert with ETV2 and HEY1, aberrantly activates NKL homeobox gene NKX2-4, which in turn represses megakaryocytic lineage factor FLI1. Interestingly, in keratinocytes, IRF6 is able to bind glucose which promotes IRF6-dimerization and thus alters its binding site selection. Here, we used OCI-M2 as a model to investigate the role of glucose level and IRF6 in leukemogenesis. Treatment of OCI-M2 with high glucose or 2-deoxy-glucose resulted in the downregulation of IRF6 and NKX2-4, and the upregulation of FLI1, indicating that glucose-mediated dimerization of IRF6 altered its reported autoactivation. The screening of this cell line for genes encoding glycolytic enzymes identified aberrant overexpression of glucose-6-phosphate isomerase (GPI) and phosphofructokinase L (PFKL), which were targeted by genomic amplification and chromothripsis-like alterations, respectively. Furthermore, GPI was activated by NKX2-4 and ETV2, and PFKL by ETV2. Finally, siRNA-mediated downregulation of PFKL resulted in elevated glucose levels, suppressed expression of IRF6 and NKX2-4, and activated FLI1. Thus, we connected an oncogenic regulatory network with deregulated glycolytic enzymes and glucose metabolism, thereby establishing a new in vitro model to develop novel therapeutic avenues in AML subsets. Full article
(This article belongs to the Special Issue Hematopoietic Cell Lines as Models for Leukemia and Lymphoma)
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Review

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13 pages, 1012 KB  
Review
From Cell Lines to Avatars: Charting the Future of Preclinical Modeling in T-Cell Malignancies
by Pier Paolo Piccaluga, Luigi Cimmino, Valeriia Tsekhovska, Pietro Cimatti, Claudia Innocenti, Sabrina Seidenari, Giulia Calafato, Floriana J. Di Paola and Giovanni Tallini
Cells 2026, 15(4), 368; https://doi.org/10.3390/cells15040368 - 19 Feb 2026
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Abstract
T-cell malignancies represent a complex spectrum of clinically and biologically heterogeneous diseases. Effective translational research and drug development are critically dependent on preclinical models that faithfully recapitulate this diversity. This review analyzes the current preclinical landscape, identifying a profound disparity between the clinical [...] Read more.
T-cell malignancies represent a complex spectrum of clinically and biologically heterogeneous diseases. Effective translational research and drug development are critically dependent on preclinical models that faithfully recapitulate this diversity. This review analyzes the current preclinical landscape, identifying a profound disparity between the clinical spectrum of T-cell neoplasms and the available in vitro tools. We demonstrate that the existing armamentarium of cell lines is heavily skewed, with an abundance of models for T-cell lymphoblastic leukemia/lymphoma (T-ALL), cutaneous T-cell lymphoma (CTCL), and anaplastic large cell lymphoma (ALCL). This skew is a direct result of a biological selection bias, as these entities are often driven by potent, TME-independent oncogenes (e.g., NOTCH1 mutations, NPM1-ALK fusions) conducive to immortalization. Conversely, the majority of peripheral T-cell lymphoma (PTCL) subtypes, which are frequently TME-dependent and clinically aggressive, remain “preclinical orphans” with few or no authenticated models. This “preclinical void” constitutes a major bottleneck, impeding mechanistic studies and therapeutic progress. We discuss the limitations of 2D cultures and highlight the necessity of adopting advanced platforms, such as patient-derived xenografts (PDX) and 3D organoid systems. These “avatar” models preserve vital tumor heterogeneity and microenvironmental context, offering superior predictive value. The systematic development and integration of these next-generation models are essential to bridge the translational gap and advance precision medicine for all patients with T-cell malignancies. Full article
(This article belongs to the Special Issue Hematopoietic Cell Lines as Models for Leukemia and Lymphoma)
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