Malignant hematopoietic cell lines: in vitro models for the study of myelodysplastic syndromes

The myelodysplastic syndromes (MDS) are clonal myeloid disorders characterized by bone marrow cell dysplasia and ineffective hematopoiesis leading to peripheral refractory cytopenias. The course of the disease ranges from a chronic status with progressively impaired hematopoiesis to rapid evolution to acute myeloid leukemia (AML). A panel of continuous malignant hematopoietic cell lines has been established from the whole spectrum of MDS variants and also from the different stages of the diseases, namely from the MDS phase or the overt leukemia post-MDS phase. Ten cell lines were derived from the various MDS subtypes; 17 cell lines were established from patients with leukemia (mainly AML) post-MDS. While most cell lines display myelocytic, monocytic or erythroid features, some cell lines carry lymphoid characteristics (precursor B-cell, B-cell, or T-cell), With regard to these lymphoid MDS-derived cell lines, more detailed authentication (prove of derivation from the assumed patient) and verification (prove of the malignant nature of the cell line and derivation from the assumed neoplastic cells) are required to validate the cell lines as true in vitro representatives of MDS and to exclude any cross-contamination with other cells or immortalization of normal bystander cells. On the other hand, lymphoid MDS-derived cell lines may attest to the clonal nature of MDS which may afflict progenitor cells giving rise to lymphoid or myelomonocytoid cells. Many of the MDS-derived cell lines carry cytogenetic and molecular genetic abnormalities typically associated with MDS: gain or loss of all or parts of chromosomes 5, 7, 8 and 20 (-5/5q-, -7/7q-, + 8, 20q-); alterations of oncogenes and tumor suppressor genes (IRF-1, p15, p16, p53, RAS, RB). In summary, the present panel of cell lines provides continuously growing cells and thus unlimited cell material for use as in vitro paradigms covering the whole spectrum of MDS-related hematopoetic malignancies. Properly authenticated and verified MDS-derived cell lines which should be made freely available will represent important research tools for the study of MDS biology.