Ikaros and leukaemia

Summary The IKZF 1 gene at 7p12.2 codes for IKAROS (also termed IKZF 1), an essential transcription factor in haematopoiesis involved primarily in lymphoid differentiation. Its importance is underlined by the fact that deregulation of IKAROS results in leukaemia in both mice and men. During recent years, constitutional as well as acquired genetic changes of IKZF 1 have been associated with human disease. For example, certain germline single nucleotide polymorphisms in IKZF 1 have been shown to increase the risk of some disorders and abnormal expression and somatic rearrangements, mutations and deletions of IKZF 1 (Δ IKZF 1 ) have been detected in a wide variety of human malignancies. Of immediate clinical importance is the fact that Δ IKZF 1 occurs in 15% of paediatric B‐cell precursor acute lymphoblastic leukaemia ( BCP ALL ) and that the presence of Δ IKZF 1 is associated with an increased risk of relapse and a poor outcome; in some studies such deletions have been shown to be an independent risk factor also when minimal residual disease data are taken into account. However, cooperative genetic changes, such as ERG deletions and CRLF 2 rearrangements, may modify the prognostic impact of Δ IKZF 1 , for better or worse. This review summarizes our current knowledge of IKZF 1 abnormalities in human disease, with an emphasis on BCP ALL .