MODEL OF MYELODYSPLASTIC SYNDROME-LIKE MYELODYSPLASIA THAT TRANSFORMSINTO SINGLE LINEAGE HEMATOPOIETIC MALIGNANCIES UPON TRANSPLANTATION -IMPLICATIONS FOR PEDIATRIC MYELODYSPLASTIC SYNDROME

The myelodysplastic syndrome (MDS) is a preneoplastic abnormal hematop oiesis over multilineage blood elements. Although a number of models a re reported for a variety of neoplastic hematopoiesis, none is availab le for the MDS-like conditions. Thus, we introduce the detailed pathol ogic features of the MDS-Like model, which transforms into a variety o f single Lineage hemopoietic malignancies. Transgenic mice carrying Si mian virus 40-large T-gene produced a variety of tumors, B cell lympho mas and other histiocytic malignancies. As we previously reported, whe n the leukemic-prone founder mice (C57BL/6 x CD1) were crossed back to C57BL/6 intensively, their descendants tended to succumb to diseases similar to human MDS and its sequelae. The majority showed the presenc e of multilineage dysplastic hemopoiesis but with a minimum potency in neoplastic nature. Huge splenomegaly was the major gross abnormality; however, neither hepatic, thymic, nor other lymphatic involvement was common. During the progressive increase in splenic weight, an extensi ve proliferation of multilineage hemopoiesis was prominent. Aiming to induce possible transition of this abnormal hemopoiesis into a single- lineage neoplasm, we developed a transplantation assay using pre-onset spleen cells and bone marrow cells from transgenic mice at an early p hase of the disease. This trial resulted in a variety of neoplastic gr owths in the recipients; not only was myelodysplastic hypercellularity seen, but also single-lineage hemopoietic malignancies. The transitio n from multilineage myelodysplasia into single-lineage hemopoiesis is reminiscent of MDS in humans. Specific implications for pediatric MDS from our expe-rimental model are discussed.