A new model of pre-B acute lymphoblastic leukemia chemically induced in rats

Objective Although B acute lymphoblastic leukemia (B-ALL) is the most common leukemia among children, no chemically inducible model of this leukemia has yet been described in vivo. Methods Leukemia was chemically induced in male WKAH/Hkm rats by a nitrosourea derivative, N-butylnitrosourea (BNU), an alkylating agent, administered orally 5 days a week for 24 weeks. Development of leukemia was monitored by clinical observation, follow-up of blood parameters, and appearance of blast cells in peripheral blood samples. The phenotype of the leukemia was determined by cytological examination, cytochemical reactions, and by immunophenotyping of bone marrow cells using various markers. The feasibility of leukemia transplantation was investigated. Clonality and karyotype analyses were also performed. Results We observed the appearance of acute leukemia in 60% of the rats treated with BNU. Of these, 65% developed pre–B-ALL, which was serially transplantable to healthy WKAH/Hkm male rats. Karyotype analysis did not reveal clonal abnormalities. Clonality determined by immunoglobulin gene rearrangement sequencing disclosed that the pre–B-ALL were mostly oligoclonal. Conclusion This new in vivo model of inducible pre–B-ALL might be useful for investigating the effects of co-initiating or promoting agents suspected to be involved in leukemia development, and for disclosing new molecular events leading to leukemogenic processes.