Acute Myeloid Leukemia (AML) Model

Acute Myeloid Leukemia (AML) Model

Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by abnormal proliferation of primitive myeloid cells in the bone marrow. The following are commonly used AML animal models and their construction methods, characteristics, and application scenarios.

I. Model Types and Core Methods

1. Cell line xenograft models (CDX)​

principle ：Transplanting human AML cell lines into immunodeficient mice to simulate leukemia proliferation and spread.

Commonly used cell lines :

Build steps :

Cell preparation : Collect cells in logarithmic growth phase and adjust the density to 1×10 ⁶ ~1×10 ⁷ cells/mL (PBS or serum-free medium).

Vaccination route :

Tail vein injection ​(Simulated systemic diffusion): 100-200 μL/piece (containing 1×10 ⁶ ~5×10 ⁶ cell).

Intraosseous injection ​(Local infiltration): Injection into the tibial or femoral medullary cavity (surgical exposure required).

Animal strains : NOD/SCID, NSG, or NOG mice (severe immunodeficient).

2. Patient-derived xenograft models (PDX)​

principle : Primary cells (bone marrow or peripheral blood) from AML patients are directly transplanted into mice to preserve tumor heterogeneity.

Advantages ：Highly simulates the patient's genetic and phenotypic characteristics, suitable for personalized treatment research.

step :

Sample processing : Ficoll density gradient centrifugation was used to separate mononuclear cells and screen CD34+/CD38- leukemia stem cells.

Transplantation method : Tail vein or bone marrow cavity injection (cell volume ≥ 1×10 ⁶ /Only).

Verification Standards :

The proportion of human cells in peripheral blood/bone marrow is >5% (flow cytometry detection of CD45+ human marker).

Pathology confirmed leukemic cell infiltration (liver and spleen enlargement).

3. Genetically Engineered Mouse Models (GEMMs)​

principle : Introducing AML-related mutations through gene editing technology (CRISPR/Cas9, transgenics).

Common models :

4. Transplantable Leukemia Model

principle : Mouse leukemia cells (such as hematopoietic stem cells transduced with MLL-AF9) are transplanted into syngeneic mice.

application ：Study the self-renewal of leukemia stem cells and their microenvironment interactions.

II. Model Monitoring and Evaluation Indicators

Peripheral blood analysis :

Flow cytometry was used to detect the proportion of human CD45+ cells.

Blood smears were used to observe the primitive/immature cell morphology.

Bone marrow/spleen pathology :

Bone marrow cytology: Giemsa staining to assess leukemic cell infiltration.

Spleen weight: The spleen weight of AML mice was significantly increased (normal mouse spleen weight ≈ 0.1g, AML can reach 0.5-1.0g).

Survival analysis : The survival time of mice was recorded (average survival time of the control group: 4-6 weeks for CDX model and 8-12 weeks for PDX model).

Molecular markers : qPCR/WB detects the expression of mutant genes (such as FLT3-ITD, NPM1).

III. Comparison of Model Advantages and Disadvantages

IV. Application Scenarios

Drug Screening : To evaluate the efficacy of chemotherapy drugs (cytarabine, daunorubicin) and targeted drugs (FLT3 inhibitors, IDH1/2 inhibitors).

Resistance mechanisms : To study the effects of drug efflux pumps (ABC transporters) and leukemia stem cell dormancy on treatment resistance.

Immunotherapy : Test the clearance effect of CAR-T cells and bispecific antibodies on AML (humanized mouse model is required).

Microenvironmental interactions ：The regulatory role of bone marrow stromal cells and vascular endothelial cells on the progression of leukemia.

V. Notes

Cell viability : Ensure cell viability > 90% before transplantation (Trypan blue staining).

Animal Ethics :

Mice should be humanely killed when they lose more than 20% of their body weight, have a significant decrease in activity, or become paralyzed.

Meets AAALAC animal welfare standards.

Monitoring frequency : Peripheral blood tests should be performed at least twice a week to avoid missing the spread of early leukemia cells.

 VI. Sample Data