Primary chromosomal rearrangements of leukemia are frequently accompanied by extensive submicroscopic deletions and may lead to altered prognosis

BCR/ABL fluorescent in situ hybridization study of chronic myeloid leukemia (CML) and Philadelphia(+) (Ph+) acute lymphoid leukemia (ALL) indicated th at approximately 9% of patients exhibited an atypical hybridization pattern consistent with a submicroscopic deletion of the 5' region of ABL and the 3' region of the BCR genes on the 9q(+) chromosome. The CML patients with d eletions had a shorter survival time and a high relapse rate following bone marrow transplant. Since deletions are associated with both Ph+ CML and AL L, it seemed probable that other leukemia-associated genomic rearrangements may also have submicroscopic deletions. This hypothesis was confirmed by t he detection of deletions of the 3' regions of the CBFB and the MLL genes i n AML M4 patients with inv(16) and in patients with ALL and AML associated with MLL gene translocations, respectively, In contrast, analysis Of the AM L M3 group of patients and AML M2 showed that similar large deletions were not frequently associated with the t(15; 17) or t(8;21) translocations. Ana lysis of sequence data from each of the breakpoint regions suggested that l arge submicroscopic deletions occur in regions with a high overall density of Alu sequence repeats. These findings are the first to show that the proc ess of deletion formation is not disease specific in leukemia and also impl icate that the presence of repetitive DNA in the vicinity of breakpoint reg ions may facilitate the generation of submicroscopic deletions. Such deleti ons could lead to the loss of one or more genes, and the associated haploin -sufficiency may result in the observed differences in clinical behavior.