Background: MicroRNAs (miRNAs) are small non-coding RNA molecules, that control gene expression by targeting messenger RNA (mRNA), via degradation or suppression of translation. Aberrant expression of microRNAs (miRs) has been proved to have a role in acute myeloid leukemias (AML)

The aim of the study was to determine expression of miR-15a in acute myeloid leukemia patients before and after chemotherapy and its influence on patient clinical outcome.

Methods: miRNAs from isolated leukemic cells were extracted using mirVanaTM miRNA Isolation kit (Ambion Inc., Carlsbad, CA, USA) following the manufacturer's protocol. Reverse transcriptase (RT) reactions were performed for mature miRNA cDNA synthesis in separate tubes using specific stem-loop RT primers and TaqMan® MicroRNATM Reverse Transcription kit (Applied Biosystems, Foster City, CA, USA). After microRNA isolation, reverse transcriptase reactions were performed, followed by cDNA amplification. The relative amount of microRNA-15a was normalized according to the reference RNU48 level. Results were considered statistically significant with p-value < 0.05.

Results: 95 patients (aged 60.2 ± 15.0, 22–90, Male = 61%) with newly diagnosed AML were included into the study. Samples of the bone marrow for miR-15a expression analysis were collected before start of chemotherapy and repeated after completed induction chemotherapy (40 patients). A control group of 20 matched patients was also taken into account. The analyzed group consisted of: 7 patients with AML M0, 34 had M1, 29 had M2, 14 had M4 and 11 had M5.

AML patients has higher miR-15a expression than control group (p=0.005633). The risk of death in AML patients was higher in patients with higher miR-15a expression on diagnosis (p=0.0430), Fig.1. Patients with lower miR-15a expression were more likely to achieve complete remission after induction chemotherapy (p=0.0130). After successful chemotherapy we observed significant drop in miR-15a expression.

Conclusions: We proved that miR-15a was upregulated in AML patients and its expression influenced remission achieving and death risk.

Figure 1.
Figure 1. Survival of AML patients depending on miR-15a expression.
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Survival of AML patients depending on miR-15a expression.

Figure 1.
Figure 1. Survival of AML patients depending on miR-15a expression.
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Survival of AML patients depending on miR-15a expression.

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Disclosures

No relevant conflicts of interest to declare.

Topics:
chemotherapy regimen, leukemia, myelocytic, acute, micrornas, chemotherapy, neoadjuvant, dna, complementary, rna, messenger, rna-directed dna polymerase, complete remission, disease remission, leukemic cells

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2014 by The American Society of Hematology
2014
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