The 5q– Syndrome

In 1956, Tjio and Levan (1) reported in a seminal observation that the correct number of chromosomes in human somatic cells was 46, not 48, as previously thought. Since then, an increasing number of malignant hematological diseases have been directly attributed to abnormalities of the number or the structure of these 46 chromosomes. The first of those disorders, of course, was chronic myeloid leukemia showing a balanced translocation of chromosomal material between chromosomes 9 and 22, reported by Nowell and Hungerford in 1960 (2). In 1973, Rowley identified the translocation t(8;21) in acute myeloid leukemia (AML), a genetic abnormality that today defines this subgroup of AML (3). One year later, in 1974, van den Berghe and colleagues reported three patients with long-standing refractory anemia, macrocytic erythrocyte indices, mild leucopenia, and normal to elevated platelet counts who showed a consistent deletion of the long arm of No. 5 chromosome (4). This disease—now called 5q– syndrome (pronounce 5q “minus” syndrome)—is classified within the myelodysplastic syndromes (MDS) and shares a number of their characteristics. The MDS are a group of bone marrow disorders derived from an abnormal hematopoietic progenitor cell (5). Because of a proliferation advantage, these abnormal stem cells have the ability to clonally expand, leading to the substitution of a variable part of normal bone marrow by malignant hematopoiesis. On the other hand, MDS are characterized by inappropriate activation of growth arrest signals that lead to a high proportion of proliferating cells finally undergoing programmed cell death (6). This impairment in cellular homeostasis explains the paradox of a hypercellular bone marrow and peripheral cytopenias often encountered in MDS. The MDS with a del(5q) chromosomal abnormality are unique because of their defining genetic lesion, their clinical and prognostic features, and their response to immunomodulatory treatments (IMiDs®). Particularly the new treatment options with IMiDs® are exciting, because they seem to target the malignant cell population independent of high-risk morphological or genetic features. This chapter will not only cover the 5q– syndrome itself, but it will also review other forms of MDS with del(5q) chromosomal abnormality that are important to the understanding of this puzzling disease.