MN1, FOXP1 and hsa-miR-181a-5p as prognostic markers in acute myeloid leukemia patients treated with intensive induction chemotherapy and autologous stem cell transplantation.

Seipel, Katja; Messerli, Christian; Wiedemann, Gertrud; Bacher, Ulrike; Pabst, Thomas (2020). MN1, FOXP1 and hsa-miR-181a-5p as prognostic markers in acute myeloid leukemia patients treated with intensive induction chemotherapy and autologous stem cell transplantation. Leukemia research, 89(106296), p. 106296. Elsevier 10.1016/j.leukres.2020.106296

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BACKGROUND

The meningioma-1 (MN1) gene is expressed in hematopoietic CD34+ cells and down-regulated during myeloid differentiation. MN1 overexpression has been linked to shorter overall and disease free survival in AML patients treated with intensive induction chemotherapy. MN1 overexpression may still be an adverse prognostic marker in AML patients treated with autologous stem cell transplant (auto-SCT) after intensive induction chemotherapy.

METHODS

We retrospectively analysed 54 peripheral blood mononuclear cell (PBMC) samples of AML patients who received auto-SCT at remission (CR1) after intensive induction chemotherapy. MN1 and putative MN1-associated mRNAs, as well as MN1-associated micro-RNAs were assessed at diagnosis in peripheral blood mononuclear cells using Taqman gene expression assays.

RESULTS

AML patients with elevated MN1 or FoxP1 gene expression at diagnosis had a significantly shorter progression-free and overall survival after intensive induction chemo-therapy and auto-SCT. The presence of the favourable risk NPM1 mutation associated with reduced MN1 gene expression. In contrast to MN1 and FOXP1, elevated expression of the putative tumor suppressive micro-RNA hsa-miR-181a-5p was predictive for positive outcome. Correlation analysis of MN1 with myeloid gene expression levels revealed association of MN1 and BMI-1, CD34, FOXP1 and MDM2 expression. Analysis of non-coding RNAs revealed an inverse correlation of MN1 with hsa-miR-20a-5p and hsa-miR-181b-5p expression.

CONCLUSIONS

MN1, FOXP1 and hsa-miR-181a-5p are prognostic markers in AML patients treated with intensive induction chemotherapy and auto-SCT. While MDM2 is a validated therapeutic target, the transcription factors MN1 and FOXP1, and the chromatin modulator BMI-1 are potential therapeutic targets in the treatment of AML. The tumor suppressor hsa-miR-181a-5p may be a candidate miRNA mimic for therapeutic use.

Item Type:

 Journal Article (Original Article)

Division/Institute:

 04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)

UniBE Contributor:

 Seipel, Katja, Wiedemann, Gertrud, Bacher, Vera Ulrike, Pabst, Thomas Niklaus

Subjects:

 600 Technology > 610 Medicine & health

ISSN:

 0145-2126

Publisher:

 Elsevier

Language:

 English

Submitter:

 Rebeka Gerber

Date Deposited:

 27 Apr 2020 08:28

Last Modified:

 02 Mar 2023 23:33

Publisher DOI:

 10.1016/j.leukres.2020.106296

PubMed ID:

 31927137

Uncontrolled Keywords:

 Acute myeloid leukemia (AML) Autologous stem cell transplantation (auto-SCT) Leukemic stem cell (LSC) Stem cell surface marker CD34 Transcription co-regulator Meningioma-1 (MN1)

BORIS DOI:

 10.7892/boris.143127

URI:

 https://boris.unibe.ch/id/eprint/143127

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