A human acute lymphoblastic leukemia line with the T(4;11) translocation as a model of minimal residual disease in SCID mice

Abstract

This study describes a new human acute lymphoblastic leukemia (ALL) cell line (ALL-PO) with the t(411) translocation established in SCID mice. The ALL-PO line can be maintained by serial transplant in SCID mice with stable immunophenotypic, molecular and karyotypic features. After intravenous (i.v.) injection ALL-PO spread systemically involving the hematopoietic organs and the central nervous system (CNS) of all mice. The homing and the progression of the disease are evaluated by histological analysis and reverse-transcriptase polymerase chain reaction (RT-PCR) amplification of the t(4;11) translocation in the bone marrow, spleen and CNS of SCID mice at different times after engraftment. Occult leukemia was detectable by PCR in the bone marrow of SCID mice as early as three days after the i.v. injection of leukemic cells whereas the first signs of involvement of the spleen and CNS appeared after 14 days; after 24 days all the mice were euthanized because they were moribund and the bone marrow, spleen and CNS showed ample infiltration by leukemic cells. The sensitivity to conventional chemotherapy was tested in this model. ALL-PO in SCID mice did not respond to treatment with vincristine or idarubicin but cyclophosphamide (150 mg kg −1 i.v., single injection) significantly increased the survival of the mice. The efficacy of such a treatment was more evident when cyclophosphamide was given in the early stages of the disease (detectable only by molecular analysis) but much less effective when the drug was administered when the disease could be detected by conventional histological analysis. The biological behavior and molecular characteristics of ALL-PO make it a good model for studying novel therapeutic strategies for a better control of minimal residual disease.