Transposable elements and Piwi‑interacting RNAs in hemato‑oncology with a focus on myelodysplastic syndrome (Review)

Abstract

Our current understanding of hematopoietic stem cell differentiation and the abnormalities that lead to leukemogenesis originates from the accumulation of knowledge regarding protein-coding genes. However, the possible impact of transposable element (TE) mobilization and the expression of P-element-induced WImpy testis-interacting RNAs (piRNAs) on leukemogenesis has been beyond the scope of scientific interest to date. The expression profiles of these molecules and their importance for human health have only been characterized recently due to the rapid progress of high-throughput sequencing technology development. In the present review, current knowledge on the expression profile and function of TEs and piRNAs was summarized, with specific focus on their reported involvement in leukemogenesis and pathogenesis of myelodysplastic syndrome. Contents1. Introduction 2. Myelodysplastic syndrome (MDS) 3. Transposable elements (TEs) 4. TE silencing by P-element-induced WImpy testis-interacting RNAs (piRNAs) 5. Methods for the exploration of TEs and piRNAs 6. TEs and piRNAs in somatic and cancer cells 7. TEs in leukemia and MDS 8. piRNAs in leukemia and MDS 9. Conclusions Myelodysplastic syndrome (MDS)MDS represents a spectrum of HSC disorders that is characterized by impaired hematopoiesis, peripheral blood cytopenia and a tendency toward leukemic transformation (3).

Mobile retroelements induced by hypomethylating agents are restricted to transpose in myeloid malignancies

“…In a model system, activation of endogenous L1s resulted in increased L1 retrotransposition and impaired leukemia cell growth in vitro and in xenotransplants. In line, a model proposed by (39) suggests that the impact of TEs activity evolves during myeloid transformation. While the increased activity of TEs and piRNAs (40) induces an immune response and leads to the elimination of leukemic cells in early-stage MDS, the leukemic cells finally escape the control of the immune system via suppression of TE/piRNA expression, resulting in the progression to high-risk MDS, accumulation of leukemic blasts, and AML.…”

The Role of Non-Coding RNAs in Myelodysplastic Neoplasms

“…Although the importance of piRNAs in other hematological malignancies such as multiple myeloma and classic Hodgkin lymphoma has gathered research interest, data on MDS have been scarce. The first study of piRNAs in bone marrow cells of patients with MDS demonstrated a higher expression (9%) of piRNAs in patients with MDS with refractory anemia (low-risk MDS) compared to patients with MDS with refractory anemia and excess of blasts-2 (high-risk MDS) and healthy controls (2% and 1%, respectively), assuming a DNA-protective role of piRNAs in lower-risk MDS [128,129]. Small non-coding RNA analysis from plasma and extracellular vesicles also showed an upregulation of specific piRNAs (hsa_piR_019914/gb/DQ597347 and hsa_piR_020450/gb/DQ598104) in MDS patients compared to controls.…”