Leukemia Animal Model Development Services
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Leukemia Animal Model Development Services

The complexity of leukemia has always placed it under research because of the prominence it holds in the realm of Medical Science. Protheragen is among the top companies focusing on animal model development for leukemia. We specialize in the human disease, replicated versions of leukemia, which are paramount in the invention and modifications of the therapies to treat leukemia.

Overview of Leukemia Animal Models

Leukemia animal models are critical for replicating the complexity of human disease in a controlled, in vivo environment. These models are not merely surrogates; they are intricate systems that allow for the study of oncogenesis, the tumor microenvironment, drug resistance, and metastasis. They offer a unique opportunity to assess the systemic effects of new therapies, including their pharmacokinetics (PK) and pharmacodynamics (PD), which is impossible to achieve in a petri dish. Furthermore, they are essential for understanding the intricate interplay between leukemic cells and the host immune system, a cornerstone of modern immuno-oncology. The proper selection and validation of an animal model are paramount to ensuring that research findings are both reproducible and translatable to human patients.

Types of cancer animal models. Fig.1 Two commonly used classification methods of cancer animal models. (Li Z., et al., 2021)

Mouse Strains for Common Leukemia Models

Leukemia research heavily relies on the use of mouse models to understand disease mechanisms and to test new therapies. The selection of an appropriate mouse strain is crucial, as it can significantly influence the relevance and accuracy of the research findings. Different mouse strains offer unique genetic backgrounds and immune system characteristics that can be tailored to various aspects of leukemia research.

Mouse Strain Characteristics
Inbred Strains C57BL/6 Background strain for spontaneous and induced mutation models
FVB/N Carry the Fv1b gene sensitive to B-type Friend Virus
BALB/c Characterized by albinism and immunodeficiency, sensitive to carcinogens
CB-17 A sub-strain of BALB/c derived from inbreeding
Mutant Strains BALB/c-nude A mutant strain of BALB/c with thymus underdevelopment, lacking T lymphocytes
SCID CB-17 SCID mice are mutants with a loss of function in B and T lymphocytes (autosomal recessive mutation)
NOD-SCID Derived from NOD mice with SCID mutation, further reduced NK cell activity.
NSG NOD/SCID/IL2Rγ−/−, derived from NOD-SCID mice with an additional IL-2 receptor gamma chain mutation, exhibiting the highest degree of immunodeficiency without mature T, B cells, or functional NK cells

Our Services

Protheragen offers a comprehensive suite of leukemia animal model development services, designed to meet the specific needs of our clients. Our team of experienced researchers and biologists works closely with clients to design and implement models that closely mimic human leukemia, ensuring relevant and reliable data.

Induced Models

Protheragen offers induced leukemia animal models primarily developed through viral induction. These models are easy to create, highly reproducible, and can be tailored to meet specific research needs. They are widely used in drug screening, toxicology, and tumor research but may not fully replicate naturally occurring human diseases.

Virus-Induced T-Cell Leukemia Animal Model

This model uses the J638 virus to induce leukemia in 615 mice. It involves injecting cell extracts from affected tissues into newborn mice, followed by subcutaneous injection of spleen cell suspensions from leukemic mice into adult mice. The L615 leukemia model is established through continuous transplantation. It's useful for studying the disease course and evaluating drug efficacy, though it has limitations in fully mimicking natural human leukemia.

Virus-Transduced Chronic Myeloid Leukemia (CML) Animal Model

Protheragen creates CML models by transducing mouse bone marrow cells with retroviral vectors expressing the bcr/abl fusion gene and transplanting them into normal mice. This model features a 90% tumor incidence rate and exhibits key characteristics of human CML, such as significant leukocytosis and splenomegaly. It is useful for studying the chronic phase of CML but may not fully replicate all aspects of the human disease.

Xenograft Models

Xenograft models are a cornerstone of leukemia research, involving the transplantation of human leukemia cells into immunodeficient mice. These models are particularly valuable for their ability to closely mimic the human disease, making them ideal for preclinical drug screening and efficacy studies. Protheragen employs various xenograft techniques, including subcutaneous, intravenous, and intramedullary injections, to develop models that accurately reflect different stages and subtypes of leukemia.

Types of Leukemia Optional Cell Lines
Acute Myeloid Leukemia (AML) AML with Minimal Differentiation (M0) MO-91, MOLM-13, MOLM-14, OCI-AML, SKNO-1, CMK-11-5
AML without Differentiation (M1) KG-1a
AML with Partial Differentiation (M2) Kasumi-1
Promyelocytic Leukemia (M3) HL-60, NB4
Myelomonocytic Leukemia (M4) ML-2
Monocytic Leukemia (M5) THP-1, MV-4-11, SHI-1
Erythroleukemia (M6) HEL, TF-1
Megakaryoblastic Leukemia (M7) M-07e
Chronic Myeloid Leukemia (CML) K562, CML-T1, KU812, BV173
Mouse Leukemia Cells C1498, EL9611

Genetically Engineered Models (GEMs)

Genetically engineered models represent a major advancement in leukemia research, providing unparalleled insights into the molecular mechanisms driving the disease. By mutating and knocking out specific genes, Protheragen creates models that can elucidate the role of specific genes in leukemia development and progression.

Model Types Conditional Knockout Mice
Model Name Ptpn11-Flox Mice
Also Known As C57BL/6-Ptpn11em1(flox)
Detailed Description This collection of strains features loxP sites that border Exon 4 of the Ptpn11 gene, enabling precise genetic manipulation. When bred with a strain that expresses Cre recombinase, these strains facilitate the conditional, tissue-specific inactivation of the Ptpn11 gene.
NCBI ID 19247
MGI ID 99511
Gene Alias Syp, Shp2, PTP1D, PTP2C, SAP-2, SHP-2, SH-PTP2, SH-PTP3, AW536184, 2700084A17Rik
Sales Status Sperm cryopreservation
Applications & Therapeutic Areas Juvenile Myelomonocytic Leukemia; Noonan Syndrome 1
Ensembl ID ENSMUSG00000043733
Pubmed Ptpn11
Human Ortholog PTPN11

Case Study

Human SKM-1 Leukemia Xenograft Model

The SKM-1 cell line was established from the peripheral blood of a patient with myelodysplastic syndrome (MDS) in the progressive leukemia phase. This cell line serves as a valuable tool for preclinical testing of leukemia therapies due to its resemblance to primary monocytes and its similarity to the mutational patterns observed in human patients. Indeed, it has been extensively utilized in the research and development of several clinical and preclinical therapeutic agents, including azacitidine and humanized anti-CD33 antibodies.

Fig 2. Changes in tumor volume and weight after injection of SKM-1 tumor cells.

At Protheragen, we recognize that each research project is unique. Our team of experienced scientists works closely with clients to design customized leukemia animal models tailored to their specific research needs. Whether it's a xenograft model, GEMM, or induced model, we ensure that the model accurately reflects the human disease of interest. If you are interested in our services, please feel free to contact us.

References

  • Li, Zhitao, et al. "Application of animal models in cancer research: recent progress and future prospects." Cancer Management and Research (2021): 2455-2475.
  • Ge, Chentao, and Caiyun Fu. "Advances in the mouse models of myeloid leukemia." Sheng wu yi xue Gong Cheng xue za zhi= Journal of Biomedical Engineering= Shengwu Yixue Gongchengxue Zazhi 36.5 (2019): 885-892.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.