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Chronic myeloid leukemia, or CML, is a clonal myeloproliferative neoplasm driven in most cases by the Philadelphia chromosome, which creates the BCR-ABL1 fusion tyrosine kinase. This constitutively active kinase promotes abnormal proliferation and survival of myeloid progenitors. CML usually presents in chronic phase with leukocytosis, granulocytic expansion, splenomegaly, fatigue, weight loss, night sweats, or incidental blood count abnormalities. It mainly affects adults, with incidence increasing with age, although pediatric cases occur. Without effective control, CML can progress to accelerated phase or blast crisis, which is more difficult to treat and associated with poor outcomes.
Tyrosine kinase inhibitors such as imatinib, dasatinib, nilotinib, bosutinib, and ponatinib have transformed CML treatment. However, residual leukemia stem cells, BCR-ABL kinase domain mutations, drug resistance, intolerance, and combination strategy selection remain active research challenges. Zebrafish CML models are most useful as rapid in vivo platforms for BCR-ABL-positive leukemia xenografts, K562-based drug response assays, imatinib resistance studies, leukemia cell migration analysis, and early prioritization of anti-leukemia compounds before mammalian testing.
Our CML platform spans BCR-ABL-positive xenografts, resistant models, primary-cell xenografts, and hematopoietic counter-screens:
| Model Name | Induction Method | Features |
|---|---|---|
| BCR-ABL-Positive Leukemia Cell Xenograft Model | Human BCR-ABL-positive leukemia cells, most commonly K562 or related CML-derived cell lines, are fluorescently labeled and microinjected into zebrafish embryos or larvae, typically into the yolk sac, perivitelline space, or circulation. After engraftment, larvae are exposed to TKIs or test compounds for 24–72 hours, followed by fluorescence imaging and phenotypic analysis. | Practical and commonly used for early in vivo CML drug efficacy testing. Supports analysis of leukemia cell survival, proliferation, dissemination, apoptosis, and response to imatinib or next-generation BCR-ABL inhibitors. |
| Imatinib-Resistant CML Xenograft Model | Imatinib-resistant K562 derivatives, BCR-ABL mutant cells, or other resistant CML cell lines are labeled and implanted into zebrafish larvae. Compounds are administered by waterborne exposure or microinjection to compare response to imatinib, dasatinib, nilotinib, ponatinib, or combination therapy. | Useful for resistance-focused studies, second-line TKI evaluation, synthetic lethality testing, and combination strategy screening. Allows rapid comparison between sensitive and resistant leukemia phenotypes in vivo. |
| Primary CML Cell / CD34+ Leukemia Progenitor Xenograft Model | Patient-derived CML mononuclear cells or enriched CD34+ leukemia progenitor cells are labeled and injected into zebrafish embryos or immunocompromised / immune-immature larvae. Engraftment, survival, localization, and treatment response are evaluated over a short assay window. | Translational model for patient-relevant drug response, leukemia stem / progenitor cell behavior, and individualized sensitivity testing. Best suited for customized projects with optimized cell preparation and imaging workflows. |
| Normal Hematopoietic Counter-Screen Model | Test compounds are evaluated in zebrafish larvae with endogenous hematopoietic reporters or normal hematopoietic phenotyping, either alone or alongside leukemia xenograft assays. | Helps distinguish anti-leukemia activity from general hematopoietic toxicity. Useful for ranking candidate BCR-ABL inhibitors, combination regimens, or novel anti-leukemia agents by therapeutic window. |
Leukemia Cell Burden & Proliferation
Engraftment, Dissemination & Migration
Drug Response & Resistance
Host Response, Hematopoietic Toxicity & Safety
In vivo zebrafish leukemia xenotransplantation for chemotherapy response. The authors used zebrafish embryos as an in vivo xenotransplantation platform for human leukemia cells. Fluorescent leukemic cells were injected into embryos, and treatment response was evaluated by changes in leukemia cell burden and distribution. The study demonstrated that zebrafish can serve as a rapid chemotherapy response assay, enabling visualization of leukemic cell viability and migration within a living host. This approach is relevant to CML model development because BCR-ABL-positive leukemia cells can be implanted and tested against TKIs or combination therapies using similar imaging-based workflows.
Fig. 1. Leukemia cell xenotransplantation in zebrafish enables in vivo assessment of chemotherapy response (Corkery DP, Dellaire G, et al., 2011).
Zebrafish leukemia stem cell xenotransplantation for quantitative chemical screening. This study developed a quantitative zebrafish xenotransplantation assay for leukemia stem cell-related screening. Leukemia cells were transplanted into zebrafish embryos, and image-based phenotyping was used to quantify cell behavior and compound effects in vivo. The model enabled chemical screening in a living vertebrate system and provided a framework for identifying compounds that affect leukemia stem cell survival or engraftment.
Fig. 2. Quantitative imaging of transplanted leukemia cells supports in vivo chemical screening in zebrafish (Zhang B, Shimada Y, et al., 2014).
Start Your Zebrafish CML Study
Our zebrafish chronic myeloid leukemia models support rapid in vivo assessment of BCR-ABL-positive leukemia cell behavior, TKI efficacy, imatinib resistance, combination therapy, and hematopoietic safety.
References
For research use only. Not intended for any clinical use.
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