Jumping Translocation of Homogeneously Staining Region Hsr(11q) in An Erythroid Leukemia: Identification of Amplified Regions by Fluorescence Hybridization, M-FISH and M-Banding

• Published in: Blood Vol. 118; no. 21; p. 4890
• Main Authors: Helias, Catherine, Gervais, Carine, Jeandidier, Eric, Lioure, Bruno, Mauvieux, Laurent
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 18.11.2011
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V118.21.4890.4890

Abstract 4890 Gene amplification is a mechanism whereby a tumor cell can increase the copy number of specific gene sequences and gain a proliferative advantage. Although amplifications are common in solid tumors, they are relatively rare in hematological neoplasms. We report here on a patient with an acute erythroid leukemia and a jumping translocation of a hsr(11q) in a complex karyotype, without MLL amplification. The patient was 40 years old when he was admitted for asthenia, peripheral blood showing pancytopenia (Hb=111G/L; neutrophils= 0.23 G/L; platelets 92 G/L), without circulating blast cells. Bone marrow was hypercellular with the presence of more than 50% of erythroid precursors and more than 20% of myeloid blast cells in non-erythroid cell population, leading to the diagnosis of erythroblastic acute leukemia. A marked dysgranulopoiesis was also detected. Conventional cytogenetics showed a complex karyotype with a del(5q), a unbalanced t(7;17) leading to partial 7q deletion and homogeneously staining regions (hsr). Fluorescence in situ hybridization confirmed the del(5q), and showed that TP53 was not deleted in the t(7;17). Multi-FISH (M-FISH) pointed out that the hsr consisted of chromosome 11 and was implicated in 3 different translocations with 3 different partner chromosomes in 3 different clones. To further characterize the amplicon and determine which bands were implicated, we used a chromosome 11 m-band probe. It revealed that the bands implicated are the same on the der(3), der(12) and der(20) and are localized between 11q23.3 and 11q25. A series of BAC probes showed that different genes, present in these regions, were amplified: ETS1, FLI1, KCNJ5, NFRKB, SNX19, HNT, OPCM, but not MLL. Amplifications of chromosome 11q usually includes MLL, but more telomeric amplicons have also been reported in AML and myelodysplatic syndromes (MDS). A very close 11q amplification was identified in 3 AML/MDS cases (Crossen et al, 1999; Tyybäkinoja et al, 2006). Also, the ETS1 oncogene was found to be rearranged and 30-fold amplified in a case of acute myelomonocytic leukaemia, in which an hsr occurred on 11q23 (Rovigatti et al, 1986). The role of chromosomal amplifications in leukemia is unclear, but it has been suggested that they are associated with rapid disease progression and short survival. Jumping translocations are an unusual phenomenon and have been rarely reported in hematological malignancies. Whether jumping translocations play a role in tumor genesis or confer a selective growth advantage on tumor cells is unknown. The combination of hsr and jumping translocations as described here are very rare in hematological malignancies. The cases of the literature (Yoshida et al, 1999) and the one presented here suggest that the 11q24-q25 region may harbor new candidate oncogenes, together with unusual chromosomal mechanisms. No relevant conflicts of interest to declare.