-7/7q-syndrome in myeloid-lineage hematopoietic malignancies: attempts to understand this complex disease entity

The recurrence of chromosomal abnormalities in a specific subtype of cancer strongly suggests that dysregulated gene expression in the corresponding region has a critical role in disease pathogenesis. - 7/7q -, defined as the entire loss of chromosome 7 and partial deletion of its long arm, is among the most frequently observed chromosomal aberrations in myeloid-lineage hematopoietic malignancies such as myelodysplastic syndrome and acute myeloid leukemia, particularly in patients treated with cytotoxic agents and/or irradiation. Tremendous efforts have been made to clarify the molecular mechanisms underlying the disease development, and several possible candidate genes have been cloned. However, the study is still underway, and the entire nature of this syndrome is not completely understood. In this review, we focus on the attempts to identify commonly deleted regions in patients with - 7/7q -; isolate the candidate genes responsible for disease development, cooperative genes and the factors affecting disease prognosis; and determine effective and potent therapeutic approaches. We also refer to the possibility that the accumulation of multiple gene haploinsufficiency, rather than the loss of a single tumor suppressor gene, may contribute to the development of diseases with large chromosomal deletions such as - 7/7q -.