A new recurrent translocation, t(5;11)(q35;p15.5), associated with del(5q)in childhood acute myeloid leukemia

Partial deletion of the long arm of chromosome 5, del(5q), is the cytogenet ic hallmark of the Sq-syndrome, a distinct subtype of myelodysplastic syndr ome-refractory anemia (MDS-RA), Deletions of 5q also occur in the full spec trum of other de novo and therapy-related MDS and acute myeloid leukemia (A ML) types, most often in association with other chromosome abnormalities. H owever, the loss of genetic material from 5q is believed to be of primary i mportance in the pathogenesis of all del(5q) disorders. In the present stud y, we performed fluorescence in situ hybridization (FISH) studies using a c hromosome 5-specific whole chromosome painting probe and a 59 subtelomeric probe to determine the incidence of cryptic translocations. We studied arch ival fixed chromosome suspensions from 36 patients with myeloid disorders ( predominantly MDS and AML) and del(5q) as the sole abnormality. In 3 AML pa tients studied, this identified a translocation of 5q subtelomeric sequence s from the del(5q) to the short arm of an apparently normal chromosome ii, FISH with chromosome 11-specific subtelomeric probes confirmed the presence of 11p on the shortened 5q. Further FISH mapping confirmed that the 5q and lip translocation breakpoints were the same in all 3 cases, between the nu cleophosmin (NPM1) and fms-related tyrosine kinase 4 (FLT4) genes on 5q35 a nd the Harvey ras-1-related gene complex (HRC) and the radixin pseudogene ( RDPX1) on 11p15.5. Importantly, all 3 patients with the cryptic t(5;11) wer e children: a total of 3 of 4 AML children studied. Two were classified as AML-M2 and the third was classified as M4. All 3 responded poorly to treatm ent and had short survival times, ranging from 10 to 18 months. Although de r(5q) is rare in childhood AML, this study indicates that, within this subg roup, the incidence of cryptic t(5;11) may be high. It is significant that none of the 24 MDS patients studied, including 11 confirmed as having 5q-sy ndrome, had the translocation. Therefore, this appears to be a new nonrando m chromosomal translocation, specifically associated with childhood AML wit h a differentiated blast cell phenotype and the presence of a del(5q). (C) 1999 by The American Society of Hematology.