1. ¹Genetics Branch, National Cancer Institute, National Institutes for Health, Bethesda, MD, USA
2. ²Comparative Molecular Pathology Unit, National Cancer Institute, National Institutes for Health, Bethesda, MD, USA
3. ³Department of Veterinary Medical Sciences, University of Maryland, College Park, MD, USA

Correspondence: Dr PD Aplan, The Genetics Branch, National Cancer Institute, National Institutes of Health, NNMC Building 8, Room 5101, 8901 Wisconsin Avenue, Bethesda, MD 20889-5105 USA. E-mails: aplanp@mail.nih.gov

Received 17 October 2007; Accepted 16 November 2007; Published online 20 December 2007.

Abstract

Chromosomal translocations are important genetic perturbations frequently associated with hematologic malignancies; characterization of these events has been a rich source of insights into the mechanisms that lead to malignant transformation. The t(10;11)(p13;q14–21) results in a recently identified rare but recurring chromosomal translocation seen in patients with ALL as well as AML, and results in the production of a CALM–AF10 fusion gene. Although the details by which the CALM–AF10 fusion protein exerts its leukemogenic effect remain unclear, emerging data suggests that the CALM–AF10 fusion impairs differentiation of hematopoietic cells, at least in part via an upregulation of HOXA cluster genes. This review discusses the normal structure and function of CALM and AF10, describes the spectrum of clinical findings seen in patients with CALM–AF10 fusions, summarizes recently published CALM–AF10 mouse models and highlights the role of HOXA cluster gene activation in CALM–AF10 leukemia.