Characterization of chromosome 11 breakpoints and the areas of deletion and amplification in patients with newly diagnosed acute myeloid leukemia

Abstract

Chromosome 11 abnormalities are found in many hematological malignancies. In acute myeloid leukemia (AML), a proto-oncogene MLL (11q23.3) is frequently altered. However, rearrangements involving other regions of chromosome 11 have been reported. Therefore, we have characterized the chromosome 11 breakpoints and common deleted and amplified areas in the bone marrow or peripheral blood cells of newly diagnosed patients with AML. Using molecular-cytogenetic methods (multicolor fluorescence in situ hybridization (mFISH), multicolor banding (mBAND), microarrays, and FISH with bacterial artificial chromosome (BAC) probes, chromosome 11 abnormalities were delineated in 54 out of 300 (18%) newly diagnosed AML patients. At least 36 different chromosome 11 breakpoints were identified; two were recurrent (11p15.4 in the NUP98 gene and 11q23.3 in the MLL gene), and three were possibly nonrandom: 11p13 (ch11:29.31-31.80 Mb), 11p12 (ch11:36.75-37.49 Mb) and 11q13.2 (68.31-68.52 Mb). One new MLL gene rearrangement is also described. No commonly deleted region of chromosome 11 was identified. However, some regions were affected more often: 11pter-11p15.5 (n = 4; ch11:0-3.52 Mb), 11p14.1-11p13 (n = 4; ch11:28.00-31.00 Mb) and 11p13 (n = 4; ch11:31.00-31.50 Mb). One commonly duplicated (3 copies) region was identified in chromosomal band 11q23.3-11q24 (n = 9; ch11:118.35-125.00 Mb). In all eight cases of 11q amplification (>3 copies), only the 5' part of the MLL gene was affected. This study highlights several chromosome 11 loci that might be important for the leukemogeneic process in AML.

Hypermethylation and down-regulation of DLEU2 in paediatric acute myeloid leukaemia independent of embedded tumour suppressor miR-15a/16-1

“…These observations are independent of the homologous miR-16 cluster embedded in SMC4 on chromosome 3q26, which shows no significant expression or DNA methylation changes in association with AML (Additional file 8). Similar results have been reported for adult CLL [32]. Taken together this data suggests an alternate mode of regulation for the miR-15a/16-1 cluster, outside of the DLEU2 promoter region.…”

“…Recent studies in adult CLL have also identified a negative correlation between DLEU2 promoter methylation ( DLEU2/Alt1) and gene expression [32]. Interestingly there was no change in gene expression for any other genes in this region (TRIM13 = 1.75 FC; DLEU1 = 1.05 FC.…”

Recurrent copy number variants associated with bronchopulmonary dysplasia

“…However, no association was observed in a subsequent study (26). The CNV at this locus have also been reported to be affected in different types of cancer (27)(28)(29). Interestingly, the LRP5 gene is located 838 kb downstream of the 11q13.2 locus, and has been shown to regulate development of lung microvessels and alveolar formation through the angiopoietin-Tie2 pathway (30).…”

Appropriate Clinical Strategies for Breast Cancer Coexisting with Acute Myeloid Leukemia in the Genomic-Molecular Era: A Case Report

“…Notably, chromosome 11 features in the cytogenetic analysis of both BC and AML [6,7]. In AML, chromosome 11 is one of the most common targets of gene amplification [8].…”

“…Amplicons on chromosome 11 may vary in size, but they usually involve the long arm of the chromosome, particularly the region 11q23, where an MLL proto-oncogene (myeloid/lymphoid leukemia or mixed-lineage leukemia (trithorax homolog [,]Drosophila)) is located [9]. In BC, nonrandom abnormalities of chromosome 11 are frequently reported, with involvement of 11p15, 11q13, and 11q23 [6]. Trisomy 11 is associated with unfavorable prognosis in AML but not with NPM1 or KIT mutation [10].…”