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Front. Oncol. | doi: 10.3389/fonc.2019.01048

Long non-coding RNAs in myeloid malignancies

  • 1Iuliu Hațieganu University of Medicine and Pharmacy, Romania
  • 2University of Texas MD Anderson Cancer Center, United States

Acute myeloid leukemia (AML) represents 80% of adult leukemias and 15-20% of childhood leukemias. AML are characterized by the presence of 20% blasts or more in the bone marrow, or defining cytogenetic abnormalities. Laboratory diagnoses of myelodysplastic syndromes (MDS) depend on morphological changes based on dysplasia in peripheral blood and bone marrow, including peripheral blood smears, bone marrow aspirate smears and bone marrow biopsies.
As leukemic cells are not functional, the patient develops anemia, neutropenia and thrombocytopenia, leading to fatigue, recurrent infections and hemorrhage. The genetic background and associated mutations in AML blasts determine the clinical course of the disease. Over the last decade, non-coding RNAs transcripts that do not codify for proteins but play a role in regulation of functions have been shown to have multiple applications in the diagnosis, prognosis and therapeutic approach of various types of cancers, including myeloid malignancies.
After a comprehensive review of current literature, we found reports of multiple long non-coding RNAs (lncRNAs) that can differentiate between AML types and how their exogenous modulation can dramatically change the behavior of AML cells. These lncRNAs include: H19, LINC00877, RP11-84C10, CRINDE, RP11848P1.3, ZNF667-AS1, AC111000.4-202, SFMBT2, LINC02082-201, MEG3, AC009495.2, PVT1, HOTTIP, SNHG5, and CCAT1. In addition, by performing an analysis on available AML data in The Cancer Genome Atlas (TCGA) , we found ten lncRNAs with significantly differential expression between patients in favorable, intermediate/normal or poor cytogenetic risk categories. These are: DANCR, PRDM16-DT, SNHG6, OIP5-AS1, SNHG16, JPX, FTX, KCNQ1OT1, TP73-AS1, and GAS5. The identification of a molecular signature based on long non-coding RNAs has the potential for have deep clinical significance, as it could potentially help better define the evolution from low-grade MDS to high-grade MDS to acute myeloid leukemia (AML), changing the course of therapy. This would allow clinicians to provide a more personalized, patient-tailored therapeutic approach, moving from transfusion-based therapy, as is the case for low-grade MDS, to the introduction of azacytidine-based chemotherapy or allogeneic stem cell transplantation, which is the current treatment for high-grade MDS.

Keywords: Myeloid malignancies, non-coding RNAs, diagnostic tool, Prognostic tool, Clinical impact

Received: 15 Jul 2019; Accepted: 26 Sep 2019.

Copyright: © 2019 Zimta, Tomuleasa, Calin and Berindan-Neagoe. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. George Calin, University of Texas MD Anderson Cancer Center, Houston, United States, gcalin@mdanderson.org