CLONALITY IN MYELODYSPLASTIC SYNDROMES

Myelodysplastic syndromes (MDS) comprises a group of acquired hematolo gical disorders which is characterized by a progressive peripheral blo od pancytopenia of one or more cell lineages. A high percentage of bla st cells in either bone marrow or peripheral blood predisposes for the transformation to acute myeloid leukemia. The clinical presentation w ith pancytopenia suggest that all cell lineages are affected by MDS. T he first experiments with X-linked restriction fragment length polymor phism (RFLP) indicated that MDS is a stem cell disorder since the clon al deletions could be detected in all cell lineages. During the 1st de cade several new molecular biological techniques such as polymerase ch ain reaction, and fluorescent in situ hybridization (FISH) were applie d to study molecular aberrations in subpopulations of cells. Molecular aberrations in all subpopulations would indicate that MDS is a stem c ell disorder. The clonal studies in MDS are equivocal. Studies involvi ng the expression of chromosomal abnormalities (standard karyotyping a nd FISH) in different cell lineages suggest that the pluripotent stem cell is not affected in MDS since the lymphoid cells usually do not ex press the abnormal karyotype. Results obtained by RFLP vary widely. So me studies indicate that the lymphoid lineage is not involved, while o ther studies find a polyclonal expression of the polymorphic genes in lymphoid cells. One study using PCR demonstrated mutations in the ras- oncogenes in T-cells as well as myeloid cells, suggesting that a commo n ancester of myeloid and lymphoid cells is affected by MDS. This revi ew discusses the different experimental approaches carried out to solv e the discussion whether MDS is a stem cell disorder.