A novel insertion ins(18;5)(q21.1;q31.2q35.1) in acute myeloid leukemia associated with microdeletions at 5q31.2, 5q35.1q35.2 and 18q12.3q21.1 detected by oligobased array comparative genomic hybridization.

backgroundNonrandom clonal chromosomal aberrations can be detected in approximately 55% of adult patients with acute myeloid leukemia (AML). Recurrent cytogenetic abnormalities play an important role in diagnosis, classification and prognosis of AML. However, several chromosomal abnormalities have not been completely determined or characterized, primarily because of their low incidence and limited amount of data.

resultsWe characterized an AML patient with a novel apparently balanced insertion ins(18;5)(q21;q31.2q35.1) that was cryptic by G-banding. The rearrangement was further examined by molecular cytogenetic methods and oligobased high-resolution array CGH (oaCGH) analysis. We show that an approximately 31.8 Mb large segment from chromosome 5 bands q31.2 to q35.1 has been inserted, by a direct mechanism, into chromosome 18 between bands q12.3 and q21.1. The insertion was unbalanced with concurrent submicroscopic deletions at 5q31.2 (approximately 0.37 Mb in size), 5q35.1q35.2 (approximately 1.98 Mb in size), and 18q12.3q21.1 (approximately 2.07 Mb in size). The microdeletions affect genes on 5q and 18q that have been associated with hematological malignancy and other cancers. A novel juxtaposition of the genes NPM1 and HAUS1 at 5q35.1 and 18q21.1, respectively, was detected by FISH analysis. Searching the literature and the Mitelman database revealed no previously reported ins(18;5) cases. Interestingly, however, two AML patients with translocation t(5;18)(q35;q21) encompassing the 5q35 and 18q21 breakpoint regions as detected in our present ins(18;5) patient have been reported.

conclusionsIt is well-known that cytogenetic abnormalities on the long arm of chromosome 5 affect hematopoiesis. However, the precise mechanism of their involvement in myeloid transformation is elusive. Our present data shed new light onto the frequent abnormalities on 5q as well as to the less frequent abnormalities observed on 18q in myeloid malignancies. In addition, we show that oaCGH analysis is a useful adjunct to revealing submicroscopic aberrations in regions of clinical importance. Reporting rare and nonrandom chromosomal abnormalities contribute to the identification of the whole spectrum of cytogenetic abnormalities in AML and their prognostic significance.