MicroRNAs Alterations in Chronic Myelomonocytic Leukemia Are Independent of Loci of Genomic Imbalance As Detected by Oligonucleotide Array CGH (oaCGH)

Chronic myelomonocytic leukemia (CMML) remains a heterogeneous group of diseases with variable patient outcomes and no well-defined targeted therapy. We studied microRNA (miRNA) expression profiles and their relation to the diagnostic and clinical parameters in CMML, and compared it their genomic DNA alteration with oligonucleotide array CGH (oaCGH).

Bone marrow samples from 22 patients with CMML were studied. Seventeen patients presented with CMML-1 and 5 with CMML-2. Nine cases had total WBC count of less than 13×10⁹/L. All cases were negative for BCR-ABL1 translocation. Microarray studies were performed using Agilent human miRNA microarrays (version 1.0) containing probes for 470 human and 64 human viral miRNAs cataloged in the Sanger database v9.1. Selected miRNA were validated using Quantitative real-time PCR using ABI TaqMan microRNA assay. Agilent human oaCGH microarrays (105k) containing probes for more than 99000 sequences were used to study genomic DNA.

None of the microRNAs that were significantly altered or were associated with predictive power in select CMML subtypes were mapped to loss or gain loci by oaCGH. Although few were mapped close to a specific amplified or deleted region.

Significantly over- or under-expressed miRNAs are found in subtypes of CMML, that do not correlate with genomic gain and loss regions as detected by high density oaCGH. Our finding might imply that multiple underlying mechanisms at level of DNA/RNA and microRNA are responsible for heterogeneity of CMMLs.

No relevant conflicts of interest to declare.