Animal models of leukemia: any closer to the real thing?

Cook, Guerry; Pardee, Timothy S.

doi:10.1007/s10555-012-9405-5

Cited by 40 publications

(38 citation statements)

References 121 publications

(116 reference statements)

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“…The impact of animal models on leukemia research cannot be overstated 4 . Nonobese diabetic (NOD) severe combined immunodeficient mice (SCID) mice with deletion in interleukin 2 receptor gamma chain (IL2Rgamma), lack functional B-and T-cells, have diminished natural killer cells, lack a functional complement system and have been proven to excellently engraft primary patient leukemia cells 4,5 .…”

Section: Introductionmentioning

confidence: 99%

PDX models reflect the proteome landscape of pediatric acute lymphoblastic leukemia but divert in select pathways

Uzozie¹,

Ergin²,

Rolf³

et al. 2019

Preprint

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Murine xenografts of pediatric leukemia are known to accurately recapitulate genomic aberrations. How this translates to the functional capacity of the proteome is unknown. Here, we studied global protein abundance, phosphorylation, and proteolytic processing in 11 pediatric B-and T-cell acute lymphoblastic leukemia patients and 19 corresponding xenografts. Protein level differences that stratified pediatric disease subtypes at diagnostic and relapse stages were largely recapitulated in xenograft models. Patient xenografts lacked multiple human leukocyte antigens, and complement proteins, and presented incomplete response mechanisms to the host immune system which is absent in the murine model. The dominant expression of MKI67 and cell cycle proteins indicated a high proliferative capacity of xenografted cells residing in the spleen. Structural genomic changes and mutations found in patients were reflected at the protein level. The post-translational modification landscape is shaped by leukemia type and host and only to a limited degree by the patient of origin. This study portrays how genomic and host factors shape protein and post-translational modification landscapes differently, and confirms murine patient-derived xenograft as competent model system while highlighting important areas of diverging biology.

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Section: Introductionmentioning

confidence: 99%

PDX models reflect the proteome landscape of pediatric acute lymphoblastic leukemia but divert in select pathways

Uzozie¹,

Ergin²,

Rolf³

et al. 2019

Preprint

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“…Models of solid tumors and leukemias have been constructed and extensively reviewed [83–87]. GEM models have significant advantages over xenograft models for evaluating immune therapies and for understanding the response of tumors in their natural microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Identifying novel therapeutic agents using xenograft models of pediatric cancer

Kurmasheva

Houghton

2016

Cancer Chemother Pharmacol

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In the USA, the overall cure rate for all childhood cancers is seventy percent, and in many patients that ultimately fail curative therapy, initial responses to current multimodality treatments (surgery, radiation therapy and chemotherapy) is good, with overall 5-year event-free survival approaching 80 %. However, current approaches to curative therapy result in significant morbidity and long-term sequelae, including cardiac dysfunction and cognitive impairment. Furthermore, dose-intensive chemotherapy with conventional agents has not significantly improved outcomes for patients that present with advanced or meta-static disease. Classical cytotoxic agents remain the backbone for curative therapy of both hematologic and solid tumors of childhood. While ‘molecularly’ targeted agents have shown some clinical activity, responses are often modest and of short duration; hence, there is a need to identify new classes of cytotoxic agent that are effective in patients at relapse and that have reduced or different toxicity profiles to normal tissues. Here we review the pediatric pre-clinical testing program experience of testing novel agents, and the value and limitations of preclinical xenograft models and genetically engineered mouse models for developing novel agents for treatment of childhood cancer.

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“…An increased number and activity of osteoclasts contribute to bone marrow necrosis or osteolytic lesions [22]. STAT5-induced cell proliferation per se is not the cause of osteocyte destruction.…”

Section: Resultsmentioning

confidence: 99%

In VivoMurine Model of Leukemia Cell-Induced Spinal Bone Destruction

Chen

Zhou

Cai

et al. 2017

BioMed Research International

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Osteolytic bone lesions can be a consequence of leukemic bone infiltration or focal bone destruction by inflammatory factors released from leukemic cells. Destructive bone lesions have a negative impact on the quality of life of leukemia patients, causing unbearable pain and, in some cases, limb paralysis. However, the mechanism, by which leukemic cells produce destructive bone lesions, and the effect of therapeutics on osteolytic lesions have not been fully elucidated yet and, thus, stand to benefit from an in vivo model. To that end, HL-60 cells were transformed by retrovirus-mediated constitutively active (CA) STAT5 expression and injected into nonobese diabetic (NOD)/SCID mice via the tail vein. After three weeks, lumbar spines were subjected to histocytometric analysis. Xenograft mice developed hind limb paralysis in 2-3 weeks, which was consistent with the consequences of spinal bone destruction by extramedullary invasion of leukemia cells. The in vivo model will improve the understanding and treatment of osteolytic bone lesions caused by myeloid leukemic cells.

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Animal models of leukemia: any closer to the real thing?

Cited by 40 publications

References 121 publications

PDX models reflect the proteome landscape of pediatric acute lymphoblastic leukemia but divert in select pathways

PDX models reflect the proteome landscape of pediatric acute lymphoblastic leukemia but divert in select pathways

Identifying novel therapeutic agents using xenograft models of pediatric cancer

In VivoMurine Model of Leukemia Cell-Induced Spinal Bone Destruction

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