Supplementary Material for: MicroRNA Profiling in Chemoresistant and Chemosensitive Acute Myeloid Leukemia

MicroRNA (miRNA) deregulation is associated with progression and treatment outcome in various types of cancers. To identify miRNAs related to therapeutic response, we applied an miRNA microarray followed by PCR verification of 33 available diagnostic bone marrow core biopsies from 33 acute myeloid leukemia patients including 15 chemoresistant and 18 chemosensitive patients. We found 3 significantly upregulated miRNAs, miR-363, miR-532-5p and miR-342-3p, related to therapeutic response (q < 0.05). Further validation of miR-532-5p and miR-363 expression by quantitative RT-PCR confirmed microarray analysis results. Genes targeted by miR-363 include <i>RGS17</i> and <i>HIPK3,</i> both reported to be associated with drug response<i>.</i

Supplementary Material for: Integrated Analysis of Gene Copy Number, Copy Neutral LOH, and microRNA Profiles in Adult Acute Lymphoblastic Leukemia

We adopted an integrated analysis of gene copy number alterations (CNAs), copy number neutral loss of heterozygosity (CNN LOH), and microRNA (miRNA) profiling in 21 adult acute lymphoblastic leukemia (ALL) patients. This study revealed the most frequent CNAs to be at chromosomes 9p, 7, and 17 and recurrent CNN LOH at 5p, 9p, and Xq. As for the most differentially expressed miRNAs, they included 8 upregulated and 14 downregulated miRNAs, of which miR-148a at 7p15.2, miR-22 at 17p13.3, miR-223 at Xq12, as well as miR-101-2 at 9p24.1 exhibited recurrent CNAs or CNN LOH. miR-101-2 was recurrently downregulated, and although the related CNN LOH was detected only in <i>BCR-ABL1</i> negative cases (2/14), deletions of miR-101-2 were observed solely in <i>BCR-ABL1</i> positive cases (4/7). Finally, <i>BCR-ABL1</i> positive cases, in contrast to negative ones, were characterized by slightly, but still significantly, higher expression levels of miR-29b

Array Comparative Genomic Hybridization Detects Chromosomal Abnormalities in Hematological Cancers That Are Not Detected by Conventional Cytogenetics

Application of array comparative genomic hybridization (aCGH) has allowed an unprecedented high-resolution analysis of cancer genomes. We developed a custom genome-wide oligonucleotide microarray interrogating 493 genes involved in hematological disorders. We analyzed 55 patients with hematological neoplasms by using this microarray. In 33 patients with apparent normal conventional cytogenetic analysis, aneuploidy or isochromosomes were detected in 12% (4 of 33) of the patients by aCGH. The chromosomal changes included trisomy of chromosomes 10, 14, and 15, tetrasomy 11, and isochromosome 17q. In 17 patients with chronic lymphocytic leukemia who were initially investigated by using a panel of standard fluorescence in situ hybridization probes, additional copy number changes that were not interrogated by the fluorescence in situ hybridization (FISH) panel were detected in 47% (8 of 17) of the patients by aCGH. Important copy number changes included gain on 2p16 involving REL and BCL11A genes, rearrangements of chromosomes 8 and 15, and trisomy of chromosomes 19 and 22. In five patients with known abnormal karyotypes, aCGH identified the origin of two marker chromosomes and detected microdeletions at five breakpoints involved in three apparent balanced translocations. Our results suggest that a subset of potentially significant genomic alterations is missed by the currently available cytogenetic techniques. This pilot study clearly demonstrates high sensitivity of oligonucleotide aCGH for potential use in diagnosis and follow-up in patients with hematological neoplasms