MV4-11 Xenograft Rat Model Service for Leukemia

The MV4-11 xenograft rat model recapitulates the aggressive biology of MLL-rearranged, FLT3-ITD–positive acute myeloid leukemia within an immunodeficient rat host, offering expanded blood volumes for pharmacokinetic profiling and scalable tissue harvest for deep biomarker analysis. Alfa Cytology constructs this model using authenticated ATCC CRL-9591 cell stocks and validated nude rat engraftment protocols, delivering reproducible tumor kinetics and integrated pharmacodynamic endpoints that advance your preclinical AML therapeutic pipeline with precision.

Overview of MV4-11 Xenograft Rat Model for Leukemia

The MV4-11 cell line (ATCC CRL-9591) was established by Rovera and colleagues from the blast cells of a 10-year-old male patient with biphenotypic B-myelomonocytic leukemia, classified under the French-American-British (FAB) system as acute myeloid leukemia M5. Genetically, the line harbors the hallmark t(4;11)(q21;q23) chromosomal translocation that generates the MLL-AF4 (KMT2A-AFF1) fusion oncoprotein, a driver of leukemogenesis frequently observed in infant and pediatric AML. In addition, MV4-11 carries an internal tandem duplication (ITD) mutation in the FLT3 receptor tyrosine kinase—an alteration present in approximately 30% of AML patients and associated with inferior prognosis—rendering the line a benchmark model for FLT3-targeted drug discovery. The cells exhibit a myelomonocytic immunophenotype (CD15+, CD33+, CD45+, CD123+) and a doubling time of approximately 32 hours under standard culture conditions.

Fig 1. MV4-11 subcutaneous transplantation model and HSN431 in vivo imaging. (Naganna, N., et al., 2019)

In vivo, MV4-11 can be engrafted into immunodeficient hosts via subcutaneous, intravenous, or orthotopic routes. Subcutaneous implantation into nude rats (e.g., Crl:NIH-Foxn1rnu) yields palpable tumors amenable to longitudinal caliper monitoring and facilitates repeated blood sampling for pharmacokinetic analysis, leveraging the larger physiological scale of rats relative to mice. The model has been extensively validated for evaluating FLT3 inhibitors such as sorafenib, sunitinib, and next-generation type I/II FLT3 inhibitors, as well as epigenetic agents targeting the MLL-menin axis or DOT1L methyltransferase. Tumors retain the characteristic MLL-AF4 fusion and FLT3-ITD mutation, ensuring molecular fidelity throughout the preclinical study window.

Cell Line Information: MV4-11

The table below summarizes the authenticated characteristics of the MV4-11 human acute myeloid leukemia cell line, compiled from ATCC repository data, Cellosaurus records, and peer-reviewed literature.

Our Services

Alfa Cytology bridges the gap between in vitro MV4-11 characterization and in vivo translational outcomes by managing every stage of xenograft construction—from authenticated cell banking and mycoplasma-free expansion through subcutaneous or systemic implantation into immunodeficient rats, longitudinal tumor monitoring, serial blood collection for pharmacokinetic analysis, and terminal histopathology with quantitative biomarker readouts. Each study is tailored to your compound's mechanism of action and conducted under accredited IACUC oversight with full GLP-aligned documentation.

Workflow of MV4-11 Xenograft Rat Model Construction

Construction of the MV4-11 xenograft rat model follows a standardized yet adaptable workflow designed to achieve high tumor take rates, consistent growth kinetics, and robust pharmacodynamic endpoints. The protocol supports both subcutaneous flank implantation for solid tumor–like mass monitoring and intravenous delivery for disseminated leukemia modeling, selected according to the scientific objective.

1. Cell Line Resuscitation & Quality Control: Cryopreserved MV4-11 stocks (ATCC CRL-9591) are thawed and expanded in complete growth medium under antibiotic-free, low-passage conditions. Cell identity is confirmed by morphology, growth curve analysis, and STR profiling against the authenticated reference (RRID: CVCL_0064). Mycoplasma testing is performed prior to in vivo use. Harvest occurs during exponential phase (2–5 × 10⁵ cells/mL); viability is assessed by trypan blue exclusion, with only suspensions exceeding 98% viability advanced to implantation. Cells are washed twice in PBS and resuspended at 5 × 10⁶ cells per 100 µL for subcutaneous injection, or at 2 × 10⁶ cells per 200 µL for intravenous tail-vein delivery.
2. Host Selection & Conditioning: Immunodeficient nude rats (Crl:NIH-Foxn1rnu, female, 6–8 weeks old, 150–200 g) are ordered from accredited vendors and acclimated for 7–10 days under specific-pathogen-free conditions. Baseline body weights and complete blood counts are recorded. Where disseminated leukemia modeling is required, rats may receive sublethal conditioning (low-dose busulfan or total body irradiation at 2.25 Gy) 24 hours prior to cell injection to enhance bone marrow engraftment, following established AML xenotransplantation protocols.
3. Tumor Cell Implantation: For subcutaneous models, 100 µL of the MV4-11 single-cell suspension (5 × 10⁶ cells) is injected into the right flank using a 25-gauge needle. For systemic leukemia models, 200 µL of cell suspension (2 × 10⁶ cells) is delivered via tail-vein injection. The subcutaneous route generates a localized tumor mass amenable to caliper measurement and intratumoral dosing, while the intravenous route models hematogenous dissemination with subsequent bone marrow, spleen, and liver infiltration.
4. Post-Implantation Monitoring & Tumor Tracking: Animals are monitored daily for clinical signs of leukemia progression including ruffled coat, hunched posture, reduced motility, and hind-limb paralysis in disseminated models. Body weights are recorded three times weekly. Subcutaneous tumors are measured twice weekly with digital calipers (volume = L × W² / 2) from first palpable detection, typically 7–10 days post-implantation. For disseminated models, peripheral blood is collected via retro-orbital bleeding or saphenous vein puncture for human CD45+ blast quantification by flow cytometry. Optional bioluminescence imaging is employed for luciferase-transduced MV4-11 variants.
5. Therapeutic Intervention & Endpoint Harvest: Upon reaching the target tumor volume (typically 100–200 mm³ for subcutaneous) or defined disease burden in disseminated models, animals are randomized into treatment and vehicle control cohorts. Test articles are administered via the sponsor-specified route—intravenous, oral gavage, intraperitoneal, or intratumoral—according to the dosing regimen. Tumor measurements and body weights continue on schedule until the study endpoint. At termination, animals are humanely euthanized. Subcutaneous tumors, bone marrow, spleen, liver, lungs, and blood are harvested. Tumor weight is recorded, tissues are digitally imaged, and samples are processed for H&E histopathology, Ki-67 proliferation index, TUNEL apoptosis scoring, FLT3 phosphorylation status by Western blot or IHC, and plasma drug-concentration profiling.

Fig 2. MV4-11 Xenograft Rat Model construction workflow.

Case Study-MV4-11 Xenograft Rat Model Development

In a recent preclinical engagement, Alfa Cytology utilized the MV4-11 subcutaneous xenograft rat model to evaluate the antitumor efficacy of a next-generation type I FLT3 inhibitor candidate. Following authenticated MV4-11 cell expansion and subcutaneous implantation into nude rats, tumors were permitted to establish for 10 days prior to randomization into vehicle, benchmark (sorafenib), and escalating dose cohorts. The candidate compound was administered via intravenous tail injection every two days for 24 days, with longitudinal tumor volume monitoring and interim body-weight assessments. Terminal analyses included H&E histopathology, Ki-67 and TUNEL dual staining to assess proliferation and apoptosis, and Western blot quantification of FLT3 autophosphorylation and downstream STAT5 signaling in tumor lysates. The dataset revealed dose-dependent tumor growth inhibition with sustained pharmacodynamic target engagement, providing the sponsor with evidence to support downstream candidate selection and IND-enabling toxicology planning.

Why Choose Alfa Cytology?

Partnering with Alfa Cytology for your MV4-11 acute myeloid leukemia program means accessing a specialized preclinical infrastructure built around authenticated leukemia cell biology, immunodeficient rat surgical expertise, and integrated pharmacodynamic analytics.

• Authenticated MV4-11 master and working cell banks are maintained under documented low-passage protocols with periodic STR verification and mycoplasma screening to ensure genetic stability and consistent tumorigenicity.
• Our surgical team is proficient in both subcutaneous flank and tail-vein intravenous implantation techniques in immunodeficient rats, achieving high tumor take rates with minimal procedure-related morbidity.
• The larger physiological scale of rats enables serial blood draws for pharmacokinetic profiling, expanded bone marrow and spleen harvest for flow cytometric blast quantification, and sufficient tumor tissue for multiplex biomarker analysis.
• Integrated molecular and histopathology capabilities include FLT3 phosphorylation assays, MLL-AF4 fusion transcript detection, Ki-67/TUNEL scoring, and human CD45+ engraftment quantification by flow cytometry.
• Study protocols are customized to your therapeutic modality—whether type I/II FLT3 inhibitors, MLL-menin disruptors, DOT1L inhibitors, or combination regimens—with clear pharmacodynamic and efficacy decision criteria.
• All in vivo work is conducted under fully accredited IACUC oversight with real-time veterinary monitoring and GLP-aligned documentation, ensuring ethical integrity and generating audit-ready data packages for regulatory submissions.

Contact Us

If your acute myeloid leukemia therapeutic pipeline demands a preclinical model that faithfully recapitulates MLL-rearranged, FLT3-ITD–positive disease biology within an immunodeficient rat host, reach out to us to discuss how Alfa Cytology can architect an MV4-11 study tailored to your development milestones. Our scientific team will review your target profile, propose a customized protocol with integrated pharmacokinetic and pharmacodynamic endpoints, and deliver a comprehensive proposal within two business days. Contact us today and accelerate your preclinical proof-of-concept with a CRO that understands the complexities of MLL-rearranged leukemia modeling.

For research use only. Not intended for any clinical use.