Genetic testing in the myelodysplastic syndromes: molecular insights into hematologic diversity

The myelodysplastic syndromes (MDS) are associated with a diverse set of acquired somatic genetic abnormalities. Bone marrow karyotyping provides important diagnostic and prognostic information and should be attempted in all patients who are suspected of having MDS. Fluorescent in situ hybridization (FISH) studies on blood or marrow may also be valuable in selected cases, such as patients who may have 5q- syndrome or those who have undergone hematopoletic stem cell transplantation. The MDS-associated cytogenetic abnormalities that have been defined by karyotyping and FISH studies have already contributed substantially to our current understanding of the biology of malignant myeloid disorders, but the pathobiological meaning of common, recurrent chromosomal lesions such as del(5q), del(20q), and monosomy 7 is still unknown. The great diversity of the cytogenetic findings described in MDS highlights the molecular heterogeneity of this cluster of diseases. We review the common and pathophysiologically interesting genetic abnormalities associated with MDS, focusing on the clinical utility of conventional cytogenetic assays and selected FISH studies. In addition, we discuss a series of well-defined MDS-associated point mutations and outline the potential for further insights from newer techniques such as global gene expression profiling and array-based comparative genomic hybridization.