Dataset Information

Profiling 25 Bone Marrow microRNAs in Acute Leukemias and Secondary Nonleukemic Hematopoietic Conditions.

ABSTRACT:

Introduction

The standard treatment of acute leukemias (AL) is becoming more efficacious and more selective toward the mechanisms via which to suppress hematologic cancers. This tendency in hematology imposes additional requirements on the identification of molecular-genetic features of tumor clones. MicroRNA (miRNA, miR) expression levels correlate with cytogenetic and molecular subtypes of acute leukemias recognized by classification systems. The aim of this work is analyzing the miRNA expression profiles in acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL) and hematopoietic conditions induced by non-tumor pathologies (NTP).

Methods

A total of 114 cytological samples obtained by sternal puncture and aspiration biopsy of bone marrow (22 ALLs, 44 AMLs, and 48 NTPs) were analyzed by real-time PCR regarding preselected 25 miRNAs. For the classification of the samples, logistic regression was used with balancing of comparison group weights.

Results

Our results indicated potential feasibility of (i) differentiating ALL+AML from a nontumor hematopoietic pathology with 93% sensitivity and 92% specificity using miR-150:miR-21, miR-20a:miR-221, and miR-24:nf3 (where nf3 is a normalization factor calculated from threshold cycle values of miR-103a, miR-191, and miR-378); (ii) diagnosing ALL with 81% sensitivity and 81% specificity using miR-181b:miR-100, miR-223:miR-124, and miR-24:nf3; and (iii) diagnosing AML with 81% sensitivity and 84% specificity using miR-150:miR-221, miR-100:miR-24, and miR-181a:miR-191.

Conclusion

The results presented herein allow the miRNA expression profile to de used for differentiation between AL and NTP, no matter what AL subtype.

SUBMITTER: Kovynev IB

PROVIDER: S-EPMC7764834 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Profiling 25 Bone Marrow microRNAs in Acute Leukemias and Secondary Nonleukemic Hematopoietic Conditions.

Kovynev Igor B IB Titov Sergei E SE Ruzankin Pavel S PS Agakishiev Mechti M MM Veryaskina Yuliya A YA Nedel'ko Viktor M VM Pospelova Tatiana I TI Zhimulev Igor F IF

Biomedicines 20201214 12

<h4>Introduction</h4>The standard treatment of acute leukemias (AL) is becoming more efficacious and more selective toward the mechanisms via which to suppress hematologic cancers. This tendency in hematology imposes additional requirements on the identification of molecular-genetic features of tumor clones. MicroRNA (miRNA, miR) expression levels correlate with cytogenetic and molecular subtypes of acute leukemias recognized by classification systems. The aim of this work is analyzing the miRNA ...[more]

PMID: 33327422

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Project description:MicroRNAs (miRNAs) are small ( approximately 22 nucleotide) non-coding RNAs whose altered expression has been associated with various types of cancers, including leukemia. In the present study, we conducted a quantitative PCR (qPCR) analysis of expression of 23 human precursor miRNAs in bone marrow specimens of 85 Chinese primary leukemia patients, including 53 acute myeloid leukemia (AML) and 32 acute lymphoblastic leukemia (ALL) cases. We show that 16 miRNAs were differentially expressed between AMLs and ALLs. Of them, eight were previously reported (i.e., miR-23a, miR-27a/b, miR-128a, miR-128b, miR-221, miR-222, miR-223, and let-7b) and eight were newly identified (i.e., miR-17, miR-20a, miR-29a/c, miR-29b, miR-146a, miR-150, miR-155, and miR-196b). More importantly, through correlating miRNA expression signatures with outcome of patients, we further show that expression signatures of a group of miRNAs are associated with overall survival of patients. Of them, three (i.e., miR-146a, miR-181a/c, and miR-221), five (i.e., miR-25, miR-26a, miR-29b, miR-146a, and miR-196b), and three (i.e., miR-26a, miR-29b, and miR-146a) miRNAs are significantly associated with overall survival (P<0.05) of the 32 ALL, 53 AML, and 40 non-M3 AML patients, respectively. Particularly, the expression signature of miR-146a is significantly inversely correlated with overall survival of both ALL and AML patients. The prognostic significance of miR-146a in AML has been confirmed further in an independent study of 61 Chinese new AML patient samples. We also identified 622 putative target genes of miR-146a that are predicted by at least three out of the five major prediction programs (i.e., TragetScan, PicTar, miRanda, miRBase Targets, and PITA). Through gene ontology analysis, we found that these genes were particularly enriched (2- to 9-fold higher than expected by chance) in the GO categories of "negative regulation of biology processes," "negative regulation of cellular processes," "apoptosis," and "cell cycle," which may be related to the association of miR-146a with poor survival.

Project description:BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs that regulate complex transcriptional networks underpin immune responses. However, little is known about the specific miRNA networks that control differentiation of specific leukocyte subsets. In this study, we profiled miRNA expression during differentiation of eosinophils from bone marrow (BM) progenitors (bmEos), and correlated expression with potential mRNA targets involved in crucial regulatory functions. Profiling was performed on whole BM cultures to document the dynamic changes in miRNA expression in the BM microenvironment over the differentiation period. miRNA for network analysis were identified in BM cultures enriched in differentiating eosinophils, and chosen for their potential ability to target mRNA of factors that are known to play critical roles in eosinophil differentiation pathways or cell identify. METHODOLOGY/PRINCIPAL FINDINGS: We identified 68 miRNAs with expression patterns that were up- or down- regulated 5-fold or more during bmEos differentiation. By employing TargetScan and MeSH databases, we identified 348 transcripts involved in 30 canonical pathways as potentially regulated by these miRNAs. Furthermore, by applying miRanda and Ingenuity Pathways Analysis (IPA), we identified 13 specific miRNAs that are temporally associated with the expression of IL-5R? and CCR3 and 14 miRNAs associated with the transcription factors GATA-1/2, PU.1 and C/EBP?. We have also identified 17 miRNAs that may regulate the expression of TLRs 4 and 13 during eosinophil differentiation, although we could identify no miRNAs targeting the prominent secretory effector, eosinophil major basic protein. CONCLUSIONS/SIGNIFICANCE: This is the first study to map changes in miRNA expression in whole BM cultures during the differentiation of eosinophils, and to predict functional links between miRNAs and their target mRNAs for the regulation of eosinophilopoiesis. Our findings provide an important resource that will promote the platform for further understanding of the role of these non-coding RNAs in the regulation of eosinophil differentiation and function.

Dataset Information

Profiling 25 Bone Marrow microRNAs in Acute Leukemias and Secondary Nonleukemic Hematopoietic Conditions.

Introduction

Methods

Results

Conclusion

Publications

Profiling 25 Bone Marrow microRNAs in Acute Leukemias and Secondary Nonleukemic Hematopoietic Conditions.

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