Murine Models of Acute Leukemia: Important Tools in Current Pediatric Leukemia Research

Jacoby, Elad; Chien, Christopher; Fry, Terry J.

doi:10.3389/fonc.2014.00095

Cited by 33 publications

(31 citation statements)

References 153 publications

(169 reference statements)

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“…These experiments support the need of a second genetic event is necessary for the development of leukaemia (Jacoby et al, 2014).…”

Section: Weight Of Evidencesupporting

confidence: 52%

Investigation into experimental toxicological properties of plant protection products having a potential link to Parkinson's disease and childhood leukaemia†

Ockleford¹,

Adriaanse²,

Berny³

et al. 2017

EFS2

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In 2013, EFSA published a literature review on epidemiological studies linking exposure to pesticides and human health outcome. As a follow up, the EFSA Panel on Plant Protection Products and their residues (PPR Panel) was requested to investigate the plausible involvement of pesticide exposure as a risk factor for Parkinson's disease (PD) and childhood leukaemia (CHL). A systematic literature review on PD and CHL and mode of actions for pesticides was published by EFSA in 2016 and used as background documentation. The Panel used the Adverse Outcome Pathway (AOP) conceptual framework to define the biological plausibility in relation to epidemiological studies by means of identification of specific symptoms of the diseases as AO. The AOP combines multiple information and provides knowledge of biological pathways, highlights species differences and similarities, identifies research needs and supports regulatory decisions. In this context, the AOP approach could help in organising the available experimental knowledge to assess biological plausibility by describing the link between a molecular initiating event (MIE) and the AO through a series of biologically plausible and essential key events (KEs). As the AOP is chemically agnostic, tool chemical compounds were selected to empirically support the response and temporal concordance of the key event relationships (KERs). Three qualitative and one putative AOP were developed by the Panel using the results obtained. The Panel supports the use of the AOP framework to scientifically and transparently explore the biological plausibility of the association between pesticide exposure and human health outcomes, identify data gaps, define a tailored testing strategy and suggests an AOP's informed Integrated Approach for Testing and Assessment (IATA).

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“…These experiments support the need of a second genetic event is necessary for the development of leukaemia (Jacoby et al, 2014).…”

Section: Weight Of Evidencesupporting

confidence: 52%

Investigation into experimental toxicological properties of plant protection products having a potential link to Parkinson's disease and childhood leukaemia†

Ockleford¹,

Adriaanse²,

Berny³

et al. 2017

EFS2

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“…In vivo murine models have provided insight and have become standard pre-clinical models in which to test novel therapeutic strategies[12–14]. While in vivo models define the gold standard they are labor intensive, time consuming, and costly to test hypotheses related to relapse of disease.…”

Section: Introductionmentioning

confidence: 99%

Bone marrow microenvironment modulation of acute lymphoblastic leukemia phenotype

Moses

Slone

Thomas

et al. 2016

Experimental Hematology

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Acute lymphoblastic leukemia (ALL) treatment regimens have dramatically improved the survival of ALL patients. However, chemoresistant minimal residual disease (MRD) that persists following cessation of therapy contributes to aggressive relapse. The bone marrow microenvironment (BMM) is an established “site of sanctuary” for ALL as well as myeloid lineage hematopoietic disease, with signals in this unique anatomical location contributing to drug resistance. Several models have been developed to recapitulate the interactions between the BMM and ALL cells. However, many in vitro models fail to accurately reflect the level of protection afforded to the most resistant sub-set of leukemic cells during co-culture with BMM elements. Pre-clinical in vivo models have advantages, but can be costly, and are often not fully informed by optimal in vitro studies. In the current report we describe an innovative extension of 2D co-culture wherein ALL cells uniquely interact with bone marrow derived stromal cells. Tumor cells in this model bury beneath primary human bone marrow derived stromal cells or osteoblasts, termed “phase dim” (PD) ALL, and exhibit a unique phenotype characterized by altered metabolism, distinct protein expression profiles, increased quiescence, and pronounced chemotherapy resistance. Investigation focused on the PD subpopulation may more efficiently inform pre-clinical design and investigation of MRD and relapse that arises from BMM supported leukemic tumor cells.

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“…[27][28][29] After 7 days, the mice were treated with IRAK inhibitor (10 mg/kg), ABT-737 (40 mg/kg), IRAK inhibitor and ABT-737 combined solution (10 mg/kg IRAK inhibitor and 40 mg/kg ABT-737), IRAK/ABT-NP (10 mg/kg IRAK inhibitor and 40 mg/kg ABT-737), or PBS as control, two times every week. 5 After 4 weeks, peripheral blood samples from each treated group of mice were taken for counting white blood cells (WBC) and staining in accordance with the Wright-Giemsa method.…”

Section: Micementioning

confidence: 99%

Cooperation of IRAK1/4 inhibitor and ABT-737 in nanoparticles for synergistic therapy of T cell acute lymphoblastic leukemia

Wu¹,

Wang²,

Qiu³

et al. 2017

IJN

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T cell acute lymphoblastic leukemia (T-ALL) is caused by clonal expansion of variant T cell progenitors and is considered as a high risk leukemia. Contemporary single chemotherapy has a limited effect due to dynamic and versatile properties of T-ALL. Here IRAK1/4 inhibitor and ABT-737 were co-encapsulated into polyethylene glycol modified poly (lactic-co-glycolic acid) nanoparticles (IRAK/ABT-NP) to enhance synergistic therapy of T-ALL. The formulation was optimized to achieve high drug loading using Box-Behnken design and response surface methodology. The optimal parameter comprised 2.98% polymer in acetonitrile, a ratio of oil phase to water phase of 1:8.33, and 2.12% emulsifier concentration. High drug loading and uniform spherical shape was achieved. In vitro release study showed sustained release of IRAK1/4 inhibitor for 72 hours as well as sustained release of ABT-737 for more than 120 hours. Uptake efficiency of IRAK/ABT-NP and induced apoptotic T-ALL fraction by IRAK/ABT-NP were much higher than the IRAK1/4 and ABT-737 combined solution. IC 50 of IRAK/ABT-NP was two-fold lower than free drug combination in Jurkat cells. Additionally, we conducted in vivo experiments in which IRAK/ABT-NP exhibited greater cytotoxicity toward T-ALL cells, the capacity to significantly restore white blood cell number in peripheral blood, and improved survival time of T-ALL mouse model compared to the IRAK1/4 and ABT-737 combined solution.

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Murine Models of Acute Leukemia: Important Tools in Current Pediatric Leukemia Research

Cited by 33 publications

References 153 publications

Investigation into experimental toxicological properties of plant protection products having a potential link to Parkinson's disease and childhood leukaemia†

Investigation into experimental toxicological properties of plant protection products having a potential link to Parkinson's disease and childhood leukaemia†

Bone marrow microenvironment modulation of acute lymphoblastic leukemia phenotype

Cooperation of IRAK1/4 inhibitor and ABT-737 in nanoparticles for synergistic therapy of T cell acute lymphoblastic leukemia

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