Impact of Bone Marrow miR-21 Expression on Acute Myeloid Leukemia T Lymphocyte Fragility and Dysfunction
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Bone Marrow and Peripheral Blood T Lymphocyte Isolation
2.3. Cell Culture and Cell Death Assay
2.4. Cell Transduction
2.5. Extracellular Vesicle Purification and Analysis
2.6. Bone Marrow Bodily Fluid Sampling and miRNA Extraction
2.7. MicroRNA Expression Profile
2.8. TaqMan miRNA Assay for Individual miRNAs
2.9. Transcriptomic Profile Array Analysis
2.10. Reverse Transcription-Quantitative Polymerase Chain Reaction
2.11. Gene Expression Array Data Analysis
2.12. Statistical Analysis
3. Results
3.1. Apoptotic Pathways Induced Fragility of Aml T Lymphocytes
3.2. Myeloid Leukemia Cell Line-Derived Extracellular Vesicles Induce T Lymphocyte Cell Death
3.3. mir-21 Expression in the Aml Bone Marrow Tumor Microenvironment
3.4. mir-21 Induces T Lymphocyte Death Through Apoptotic Pathways
3.5. mir-21 Expression Increases T Cell Immunosuppressive Phenotypic Markers
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Clinical details of AML patients (27) | Number |
---|---|
Sex and age | |
Males | 13 |
Females | 14 |
Age < 55y | 9 |
Age ≥ 55y | 18 |
Classification of AML patients | |
Cytogenetic abnormalities | |
Normal Karyotype | 3 |
Chromosome 9 deletion | 2 |
Inversion (16) MYH11-CBFB | 2 |
Translocation (t8;21) | 2 |
Translocation (t15;17) | 3 |
Translocation (X:21) (p11;q22) | 1 |
trisomy 8 | 1 |
complex Karyotype | 1 |
WHO 2016 system | |
AML with recurrent genetic abnormalities (t8;21) | 2 |
AML with recurrent genetic abnormalities (inv 16) | 2 |
AML with recurrent genetic abnormalities (t15;17) | 3 |
Acute monoblastic/monocytic leukemia | 1 |
Pure erythroid leukemia | 1 |
AML not otherwise specified (NOS) | 15 |
unknown | 3 |
ELN 2017 genetic risk stratification | |
Favorable | 10 |
Intermediate | 3 |
Adverse | 10 |
unknown | 4 |
EV-Derived miRNAs | K562 Mean Ct (SD) | KG1 Mean Ct (SD) | HL60 Mean Ct (SD) |
---|---|---|---|
hsa-miR-145 | 28.547 (1.034) | 29.522 (1.064) | 29.522 (1.064) |
hsa-miR-484 | 27.792 (0.812) | 28.481 (1.114) | 28.481 (1.114) |
hsa-miR-29a | 28.463 (1.235) | 27.747 (0.848) | 27.747 (0.848) |
hsa-miR-25 | 27.750 (1.350) | 27.739 (0.707) | 27.739 (0.707) |
hsa-miR-425-5p | 29.410 (1.167) | 27.454 (1.213) | 27.454 (1.213) |
hsa-miR-186 | 27.534 (1.156) | 26.930 (1.056) | 26.930 (1.056) |
hsa-miR-532 | 29.952 (1.000) | 26.685 (0.619) | 26.685 (0.619) |
hsa-miR-210 | 26.659 (1.228) | 26.656 (0.,904) | 26.656 (0.904) |
hsa-miR-27a | 29.696 (1.184) | 26.572 (0.798) | 26.572 (0.798) |
hsa-miR-320 | 25.836 (0.844) | 26.540 (1.093) | 26.540 (1.093) |
hsa-miR-15b | 28.530 (1.134) | 25.739 (0.715) | 25.739 (0.715) |
hsa-miR-494 | 26.762 (1.276) | 25.598 (1.387) | 25.598 (1.387) |
hsa-let-7e | 29.536 (1.014) | 25.354 (0.876) | 25.354 (0.876) |
hsa-miR-19a | 29.703 (1.226) | 24.629 (0.756) | 24.629 (0.756) |
hsa-miR-483-5p | 26.502 (1.077) | 24.592 (0.913) | 24.592 (0.913) |
hsa-miR-20b | 28.791 (0.746) | 23.807 (0.999) | 23.807 (0.999) |
hsa-miR-30c | 24.754 (0.762) | 23.778 (0.975) | 23.778 (0.975) |
hsa-miR-21 | 27.538 (1.215) | 23.750 (1.082) | 23.750 (1.082) |
hsa-miR-16 | 26.564 (1.331) | 23.693 (0.867) | 23.693 (0.867) |
hsa-miR-30b | 26.688 (0.844) | 23.656 (0.811) | 23.656 (0.811) |
hsa-miR-92a | 24.688 (1.311) | 23.539 (1.175) | 23.539 (1.175) |
hsa-miR-221 | 29.812 (1.008) | 23.398 (1.106) | 23.398 (1.106) |
hsa-miR-146b | 21.782 (1.058) | 22.850 (1.152) | 22.850 (1.152) |
hsa-miR-142-3p | 28.549 (1.094) | 22.804 (0.799) | 22.804 (0.799) |
hsa-miR-191 | 22.488 (0.917) | 22.626 (1.328) | 22.626 (1.328) |
hsa-miR-342-3p | 24.720 (0.773) | 22.442 (1.177) | 22.442 (1.177) |
hsa-miR-222 | 27.684 (0.892) | 21.850 (1.156) | 21.850 (1.156) |
hsa-miR-24 | 26.898 (1.107) | 21.815 (1.257) | 21.815 (1.257) |
hsa-miR-20a | 24.698 (0.668) | 21.463 (1.113) | 21.463 (1.113) |
hsa-miR-17 | 23.745 (1.036) | 19.910 (1.037) | 19.910 (1.037) |
hsa-miR-106a | 23.721 (0.986) | 19.773 (0.746) | 19.773 (0.746) |
hsa-miR-223 | 20.705 (0.886) | 18.706 (1.167) | 18.706 (1.167) |
hsa-miR-19b | 23.768 (1.284) | 18.478 (0.980) | 18.478 (0.980) |
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Share and Cite
Moussa Agha, D.; Rouas, R.; Najar, M.; Bouhtit, F.; Fayyad-Kazan, H.; Lagneaux, L.; Bron, D.; Meuleman, N.; Lewalle, P.; Merimi, M. Impact of Bone Marrow miR-21 Expression on Acute Myeloid Leukemia T Lymphocyte Fragility and Dysfunction. Cells 2020, 9, 2053. https://doi.org/10.3390/cells9092053
Moussa Agha D, Rouas R, Najar M, Bouhtit F, Fayyad-Kazan H, Lagneaux L, Bron D, Meuleman N, Lewalle P, Merimi M. Impact of Bone Marrow miR-21 Expression on Acute Myeloid Leukemia T Lymphocyte Fragility and Dysfunction. Cells. 2020; 9(9):2053. https://doi.org/10.3390/cells9092053
Chicago/Turabian StyleMoussa Agha, Douâa, Redouane Rouas, Mehdi Najar, Fatima Bouhtit, Hussein Fayyad-Kazan, Laurence Lagneaux, Dominique Bron, Nathalie Meuleman, Philippe Lewalle, and Makram Merimi. 2020. "Impact of Bone Marrow miR-21 Expression on Acute Myeloid Leukemia T Lymphocyte Fragility and Dysfunction" Cells 9, no. 9: 2053. https://doi.org/10.3390/cells9092053