How animal models of leukaemias have already benefited patients

Ablain, Julien; Nasr, Rihab; Zhu, Jun; Bazarbachi, Ali; Lallemand-Breittenbach, Valérie

doi:10.1016/j.molonc.2013.01.006

Cited by 7 publications

(4 citation statements)

References 77 publications

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“…Both studies highlight the importance of a humanized microenvironment for studying human leukemic niches in animals; however, technical advances are still required in order to achieve an identical human immune function in recipient animals (e.g., HLA alleles matched to donor human cells, development of lymphoid architecture, identification of human-specific factors needed for optimal human cell function that are absent in mice, among others). It is also necessary to prevent the development of graft vs. host disease, which occurs in many of the human immune engrafted models, and validate the results obtained in the models described here [146,157].…”

Section: In Vivo Rodent Modelssupporting

confidence: 53%

In Vitro and In Vivo Modeling of Normal and Leukemic Bone Marrow Niches: Cellular Senescence Contribution to Leukemia Induction and Progression

Salazar-Terreros

Vernot

2022

IJMS

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Cellular senescence is recognized as a dynamic process in which cells evolve and adapt in a context dependent manner; consequently, senescent cells can exert both beneficial and deleterious effects on their surroundings. Specifically, senescent mesenchymal stromal cells (MSC) in the bone marrow (BM) have been linked to the generation of a supporting microenvironment that enhances malignant cell survival. However, the study of MSC’s senescence role in leukemia development has been straitened not only by the availability of suitable models that faithfully reflect the structural complexity and biological diversity of the events triggered in the BM, but also by the lack of a universal, standardized method to measure senescence. Despite these constraints, two- and three dimensional in vitro models have been continuously improved in terms of cell culture techniques, support materials and analysis methods; in addition, research on animal models tends to focus on the development of techniques that allow tracking leukemic and senescent cells in the living organism, as well as to modify the available mice strains to generate individuals that mimic human BM characteristics. Here, we present the main advances in leukemic niche modeling, discussing advantages and limitations of the different systems, focusing on the contribution of senescent MSC to leukemia progression.

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Section: In Vivo Rodent Modelssupporting

confidence: 53%

In Vitro and In Vivo Modeling of Normal and Leukemic Bone Marrow Niches: Cellular Senescence Contribution to Leukemia Induction and Progression

Salazar-Terreros

Vernot

2022

IJMS

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“…Mice can be genetically engineered to express dominant oncogenes in the mouse germline or by mutation of tumor suppressor genes. AML was amongst the earliest diseases to be modelled using transgenic animals owing to its relative genetic simplicity [ 219 , 220 ]. Transgenic models can be produced by several methods and have been reviewed elsewhere [ 221 ].…”

Section: Models Of Acute Myeloid Leukemiamentioning

confidence: 99%

Modelling acute myeloid leukemia (AML): What’s new? A transition from the classical to the modern

Dozzo

Galvin

Shin

et al. 2022

Drug Deliv. and Transl. Res.

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Acute myeloid leukemia (AML) is a heterogeneous malignancy affecting myeloid cells in the bone marrow (BM) but can spread giving rise to impaired hematopoiesis. AML incidence increases with age and is associated with poor prognostic outcomes. There has been a disconnect between the success of novel drug compounds observed in preclinical studies of hematological malignancy and less than exceptional therapeutic responses in clinical trials. This review aims to provide a state-of-the-art overview on the different preclinical models of AML available to expand insights into disease pathology and as preclinical screening tools. Deciphering the complex physiological and pathological processes and developing predictive preclinical models are key to understanding disease progression and fundamental in the development and testing of new effective drug treatments. Standard scaffold-free suspension models fail to recapitulate the complex environment where AML occurs. To this end, we review advances in scaffold/matrix-based 3D models and outline the most recent advances in on-chip technology. We also provide an overview of clinically relevant animal models and review the expanding use of patient-derived samples, which offer the prospect to create more “patient specific” screening tools either in the guise of 3D matrix models, microphysiological “organ-on-chip” tools or xenograft models and discuss representative examples. Graphical abstract

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“…Notably, another classical transgenic model for APL associated with a PLZF-RARA fusion gene derived from t(11;17)(q23;q21) revealed that ATRA was unable to induce remission in mice, faithfully recapitulating the clinical response in the respective patients [55]. We list some of the most important classical transgenic AML models in Table 1 and refer to respective review articles [56,57,58]. Unfortunately, the classical transgenic mouse approach is inefficient, technically challenging, time- and cost-consuming and as illustrated by the APL mouse model and others, unable to recapitulate the desired phenotypes [59].…”

Section: Genetically Engineered Mouse Modelsmentioning

confidence: 99%

Murine Models of Acute Myeloid Leukaemia

Almosailleakh

Schwaller

2019

IJMS

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Acute myeloid leukaemia (AML) is a rare but severe form of human cancer that results from a limited number of functionally cooperating genetic abnormalities leading to uncontrolled proliferation and impaired differentiation of hematopoietic stem and progenitor cells. Before the identification of genetic driver lesions, chemically, irradiation or viral infection-induced mouse leukaemia models provided platforms to test novel chemotherapeutics. Later, transgenic mouse models were established to test the in vivo transforming potential of newly cloned fusion genes and genetic aberrations detected in patients’ genomes. Hereby researchers constitutively or conditionally expressed the respective gene in the germline of the mouse or reconstituted the hematopoietic system of lethally irradiated mice with bone marrow virally expressing the mutation of interest. More recently, immune deficient mice have been explored to study patient-derived human AML cells in vivo. Unfortunately, although complementary to each other, none of the currently available strategies faithfully model the initiation and progression of the human disease. Nevertheless, fast advances in the fields of next generation sequencing, molecular technology and bioengineering are continuously contributing to the generation of better mouse models. Here we review the most important AML mouse models of each category, briefly describe their advantages and limitations and show how they have contributed to our understanding of the biology and to the development of novel therapies.

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How animal models of leukaemias have already benefited patients

Cited by 7 publications

References 77 publications

In Vitro and In Vivo Modeling of Normal and Leukemic Bone Marrow Niches: Cellular Senescence Contribution to Leukemia Induction and Progression

In Vitro and In Vivo Modeling of Normal and Leukemic Bone Marrow Niches: Cellular Senescence Contribution to Leukemia Induction and Progression

Modelling acute myeloid leukemia (AML): What’s new? A transition from the classical to the modern

Murine Models of Acute Myeloid Leukaemia

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