Leukemia Xenograft Model

Altogen Labs validated Leukemia Xenograft animal models:

Xenotransplantation studies have been a backbone of oncology research for four decades, and provide an effective research and evaluation environment for novel pharmaceutical compounds. Typically, these studies involve the implantation of tumorigenic human cell lines into immunocompromised mice, providing scientists with an in vivo model of tumor behavior in which to perform experiments including screening of novel cancer therapies, studies of cell behavior, and examination of metastasis. Patient-derived xenografts are a fundamental part of in vivo pharmacological research, aiding in the translation from benchtop to bedside.

Leukemia is a type of cancer that usually begins in bone marrow and affects various types of blood cells. Symptoms of leukemia include excessive bleeding and bruising, fatigue, fever and frequent infections. Risk factors include genetics, smoking, radiation, prior chemotherapy and Down syndrome. Leukemia detection methods include blood tests and bone marrow biopsies. Types of leukemia are divided into four main groups. First is acute lymphoblastic leukemia (ALL) which is particularly dangerous when it spreads to the central nervous system. Treatment usually requires induction chemotherapy for bone marrow remission followed by consolidation therapy to target remaining leukemia cells and finally prophylaxis and maintenance treatments to prevent recurrence. Second, acute myeloid leukemia (AML) affects the myeloid line of blood cells where normal blood cells are replaced by leukemic cells which make people extremely sensitive to infections. Third, chronic lymphoblastic leukemia (CLL) are often low-grade that do not benefit from treatments which then have to be directed towards suppressing rather than eradicating the disease. Often combination chemotherapy with either chlorambucil or cyclophosphamide with a corticosteroid is used, and in younger patients a bone marrow transplantation is a potential option for a permanent cure. Lastly, chronic myeloid leukemia (CML) are primarily able to manage the cancer for at least 5 years with oral at home chemotherapy regimens (e.g. with imatinib/Gleevec). Acute leukemias are when immature blood cell levels increase rapidly causing unhealthy cells to appear. Timely treatment is critical in acute leukemias due to the rapid rate of progression of malignant cells. Chronic leukemias are when abnormal mature white blood cells accumulate excessively. These cancers progress slowly over the course of months or years and do not require immediate treatment. Prognosis is a 5 year survival rate of 57% in the United States and depends greatly on severity of anemia and metastasis.

Using human xenograft models of leukemia, as previously mentioned, is a powerful research tool, and there are several models of leukemia to choose from. There are links above to some of the most common tissue culture models that Altogen Labs has available, summarized in the table below. Models are often selected based on morphology, genetics, histology, early vs. late stage phenotype, invasive/aggressive properties, and abnormal protein expressions (usually relating to cell cycle, apoptosis, growth and angiogenesis). The goal of xenografts and murine models is to mirror human pathology and disease as closely as possible so that accurate insights into cellular events are achieved. This aspect is particularly critical with preclinical drug testing for accurately evaluating compound efficacy.

Cell Line	Characteristics
HL-60	· Human AML isolated from peripheral blood cells· Promyeloblast cell type that can spontaneously differentiate after stimulation · Pseudodiploid karyotype · Exhibit phagocytotic activity · Expresses myeloperoxidase and tumor necrosis factor (after phorbol myristic acid stimulation) and is negative for C-EBP-alpha
K-562	· Human CML derived from a pleural effusion of bone marrow of a patient in blast crisis· Highly undifferentiated lymphoblast cell type and can develop characteristics similar to erythrocytes, monocytes or granulocytes · Often used for the natural killer assay · EBNA negative
MOLM13	· Derived from the peripheral blood from a patient with acute myeloid leukemia relapse· Hyperdiploid karyotype · Cells display features of AML as well as myelodysplatic syndromes (MDS) · Positive for CD4, CD13, CD15, CD33 and cyCD68 · Have an internal tandem duplication for FLT3 which is not expressed

Cell Line

Characteristics

MOLT-4

· Human T-lymphoblast type leukemia

· Hypertetraploid karyotype

· Taken from a patient in relapse who had received multidrug chemotherapy

· G–A mutation in the p53 codon 248

· P53 is not expressed

· Immunoglobulin is not expressed

· Negative for the Epstein-Barr virus

· Expresses antigens CD1, 2, 3A, 3B, 3C, 4, 5, 6, and 7

· Expresses high levels of terminal deoxynucleotidyl transferase (TdT)

Altogen Labs is one of the leading biology contract research organization (CRO) based in Austin, Texas. Altogen Labs provides years of expert research in xenograft experiments taking advantage of the comprehensive expertise the company has developed in the use of human tumor xenografts for research and clinical purposes. Altogen Labs offers a complete suite of laboratory services, including:

xenotransplantation study design
selection of appropriate cancer model/cell line
host animal selection
subcutaneous or orthotopic xenografting
daily observation of experimental subjects
post-experiment analysis, including serum collection and histology

Mouse strains available at Altogen Labs:

Mouse type	T cells	B cells	NK cells	Coat	Other Notes
CD1	No	Yes	Yes	White/albino	Outbred
B6	Yes	Yes	Yes	White/albino	Inbred
Balb/c	No	Yes	Yes	Nude, albino	Inbred
Balb/SCID	No	No	Yes	White	Inbred
NOD/SCID	No	No	Impaired	White	Inbred
Nu/nu	No	Yes	Yes	Nude	Outbred
CD57BL	Yes	Yes	Yes	Dark brown/black	Inbred
CB17	Yes	Yes	Yes	White	Inbred
NSG	No	No	No	White	Inbred
Swiss Nude	No	Yes	Yes	Nude	Outbred

About the models

CD1

This model originates from a non-inbred Swiss stock of the 1920s from the Centre Anticancerux Romand (Lausanne, Switzerland). Outbred stocks are generally used for their genetic variability.

This strain of mouse arose from a spontaneous mutation in the C57BL/6 strain resulting in a coisogenic albino mutant. These mice have a mutant tyrosinase gene.

Balb/c

This strain of nude mouse was developed in the 1980s through many crosses and backcrosses and remains to be an inbred model. Balb/c mice do not have a thymus and therefore cannot produce T-cells and are considered immunodeficient. Balb/c mice are often used for their easy breeding and similar weights (low-variation) of males and females. They are also used for monoclonal antibody production.

Balb/SCID

This mouse model lacks functioning T and B cells but do have functioning NK cells which limits engraftment. These mice are sensitive to irradiation and have functioning macrophages, dendritic cells and complement activity. Some cancer cell lines show improved engraftment over nude models in Balb/SCID mice.

NOD/SCID

The homozygous SCID mutation results in impaired T cell and B cell lymphocyte development. The NOD characteristic results in impaired natural killer cell function. NOD/SCID mice also lack macrophage and dendritic cell activity as well as reduced complement activity. These mice have a non-obese diabetic and insulitis background and low cytokine production. NOD/SCID mice exhibit a 36-week median survival due to the development of thymic lymphomas, which limits their use to short-term experiments.

Nu/nu

These mice originate from the National Institute of Health (NIH). Originally thought to be BALB/C congenic mice, once it was discovered that these mice were outbred they were determined to be of their own strain. These mice do not have a thymus, or T-cells, and are nude immunodeficient models.

CD57BL/6

This laboratory mouse strain was the 2^nd mammalian species to ever have its genome published in entirety. They originate from the Bussey Institute for Research in Applied Biology in 1921. These mice are often selected for easy breeding and availability of congenic strains. These mice are particularly sensitive to odors, noise, pain, cold, alcohol and morphine addiction.

CB17

CB17 mice are of a congenic strain that carry the immunoglobulin heavy chain allele (Igh-1b) from a C57BL/Ka on a BALB/c background. They are an ideal control for the CB17/SCID immunodeficient mouse model

NSG

Also known as NOD scid gamma, these mice are deficient in NK, T and B cells as well as multiple cytokine pathways. They also have reduced dendritic cell function and defective macrophage activity and lack a complement system. They are one of the most immunodeficient models available and unlike NOD/SCID mice, NSG mice do not develop thymic lymphomas and can be used for long-term experiments.

Swiss Nude

These mice originate from the 1974 Gustave Roussy Institute (Villejuif, France) Swiss stock. They are T cell deficient, nude and albino.

All laboratory studies are performed by experienced personnel in a GLP-compliant and IACUC-regulated facility in Austin, Texas. Please contact us at info@altogenlabs.com, or call 512-433-6177 to discuss xenograft study details.