Abstract

Myelodysplastic syndromes are a group of clonal diseases of hematopoietic stem cells and are characterized by multilineage dysplasia, ineffective hematopoiesis, peripheral blood cytopenias, genetic instability and a risk of transformation to acute myeloid leukemia. Some patients with non-Hodgkin lymphomas (NHLs) may have developed secondary myelodysplasia before therapy. Bone marrow (BM) hematopoiesis is regulated by a spectrum of epigenetic factors, among which microRNAs (miRNAs) are special. The aim of this work is to profile miRNA expression in BM cells in untreated NHL patients with secondary myelodysplasia. A comparative analysis of miRNA expression levels between the NHL and non-cancer blood disorders samples revealed that let-7a-5p was upregulated, and miR-26a-5p, miR-199b-5p, miR-145-5p and miR-150-5p were downregulated in NHL with myelodysplasia (p < 0.05). We for the first time developed a profile of miRNA expression in BM samples in untreated NHL patients with secondary myelodysplasia. It can be assumed that the differential diagnosis for blood cancers and secondary BM conditions based on miRNA expression profiles will improve the accuracy and relevance of the early diagnosis of cancerous and precancerous lesions in BM.

Highlights

  • We analyzed the expression of 798 miRNA from non-Hodgkin’s lymphomas (NHLs), Myelodysplastic syndromes (MDSs) and non-cancerous blood diseases (NCBD), using the NanoString nCounter analysis system

  • We performed a comparative analysis of the number of these miRNAs between MDS, NHL (−MD), NHL (+MD) (−A), NHL (+MD)

  • We developed a profile of miRNA expression in (1) MDS patients and (2) NHL patients with and without secondary myelodysplasia against NCBD peers

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Summary

Introduction

Myelodysplastic syndromes (MDSs) are a group of clonal diseases of hematopoietic stem cells and are characterized by multilineage dysplasia in immature myeloid cells, ineffective hematopoiesis, peripheral blood (PB) cytopenias and a risk of transformation to acute myeloid leukemia (AML) [1].According to the Surveillance, Epidemiology and End Results (SEER), the MDS incidence in the USA in 2012–2017 was 28,032 and the majority of the affected people were above 70 years of age [2].Diagnosing MDS is challenging; for example, at early stages, it is quite difficult to differentiate minor morphological changes associated with dysplasia from other bone marrow (BM) deficiencies [3]. can MDS be de novo, and secondary, which cancer patients develop following treatment with cytostatic agents (t-MDS) [4]. Myelodysplastic syndromes (MDSs) are a group of clonal diseases of hematopoietic stem cells and are characterized by multilineage dysplasia in immature myeloid cells, ineffective hematopoiesis, peripheral blood (PB) cytopenias and a risk of transformation to acute myeloid leukemia (AML) [1]. Diagnosing MDS is challenging; for example, at early stages, it is quite difficult to differentiate minor morphological changes associated with dysplasia from other bone marrow (BM) deficiencies [3]. Can MDS be de novo, and secondary, which cancer patients develop following treatment with cytostatic agents (t-MDS) [4]. Secondary MDS is associated with symptomatic PB cytopenias and abnormal BM cell morphology resembling those observed in primary MDS. One important discovery was the fact that patients with non-Hodgkin’s lymphomas (NHLs) can develop myelodysplasia even before the onset of treatment [5].

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