Analysis of balanced rearrangements of chromosome 6 in acute leukemia : clustered breakpoints in q 22 - q 23 and possible involvement of c - MYB

Recurrent chromosomal translocations are important diagnostic and prognostic markers contributing to the management of patients with a variety of hematologic malignancies. Moreover, the molecular characterization of breakpoints from such rearrangements has led to the identification of oncogenes and to the design of novel therapeutic approaches and sensitive polymerase chain reaction (PCR)based systems for monitoring residual disease. In addition to recognized recurrent abnormalities, numerous sporadic translocations have been reported and these may activate known or hitherto unrecognized oncogenes, contribute to leukemia through other mechanisms or be incidental to the malignant process. Among hematologic malignancies, balanced rearrangements of the long arm of chromosome 6 (6q) are most common in acute myeloid leukemia (AML) and frequently involve translocation with 11q23. Two recurrent t(6;11) translocations have been described and these fuse MLL (multi lineage leukemia) to AF6 at band 6q27 or AF6q21 at band 6q2. The t(6;8)(q27;p11) that fuses the FGFR1 (fibroblast growth factor receptor 1) gene to FOP (FGFR1 oncogene partner) is seen in rare cases of myeloproliferative syndrome. Other translocations of 6q have been reported in patients with AML or acute lymphoblastic leukemia (ALL) although none has been cloned and most are currently considered sporadic (Mitelman Database of Chromosome Aberrations in Cancer; available at URL http://cgap.nci.nih.gov/Chromosomes/Mitelman. By contrast with translocations, cytogenetically visible deletions of 6q are common in lymphoid malignancies, with a reported incidence of 4-13% in ALL, 13-15% in lymphomas and 4.5% in chronic lymphocytic leukemia. Both fluorescence in situ hybridization (FISH) and microsatellite analysis have been used to define region(s) of minimal deletion (RMD) in ALL and lymphomas. Based on these studies several candidate tumor suppressor genes have been proposed but evidence in support of a leukemia protective role for any of these has From the Haematology Department, Royal Free and University College School of Medicine, Rowland Hill Street, London NW3 2PF, UK (PBS, LF); Leukaemia Research Fund Cytogenetics Group, Cancer Sciences Division, University of Southampton, Southampton, UK (CJH); Department of Haemato-Oncology, Palacky University Hospital, Olomouc, Czech Republic (MJ).