Clinical Significance of microRNAs in Hematologic Malignancies and Hematopoietic Stem Cell Transplantation
Abstract
:Simple Summary
Abstract
1. Introduction
2. MicroRNA in Hematopoiesis and Hematologic Malignancies
2.1. MiRNA Biology
2.2. The Role of microRNAs in Normal Hematopoiesis
2.3. MicroRNA Dysregulation in Malignant Hematopoiesis
2.4. Aberrant microRNA Expressions in Diagnosis, Prognosis, and Monitoring of Therapy
3. MicroRNA in Hematopoietic Stem Cell Transplantation
3.1. Hematopoietic Stem Cell Transplantation
3.2. MicroRNA and Graft-Versus-Host Disease
3.3. MicroRNA and Post-HSCT Patient Outcomes
4. Investigating the Therapeutical Potential of the miRNA-Based Approach in Hemato-Oncology
5. Conclusions and Future Directions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Malignancy | miRNA | miRNA Expression Level | Target Genes | Study Type | miRNA Function/Clinical Consequence | Reference |
---|---|---|---|---|---|---|
AML | miR-3662 | DOWN | IKBKB | AM, PS (N = 20), TC | Acceleration of the growth and colony formation of HP cells, survival of leukemic cells | [58] |
miR-9 | UP | RHOH RYBP + 15 other potential targets | AM CL PS (N = 85) | Increasing cell survival and decreasing apoptosis | [82] | |
miR-29b | DOWN | MCL-1, CXXC6, CDK6 | AM, CL, PS (N = 100) | Cell growth and anti-apoptotic activity | [83] | |
miR-126 | UP | SLC9A7, ABCG1, MEF2C, RBMPS, LYZ, CSTA, HAL | AM, CL, PS (N = 6) | Cell growth and anti-apoptotic activity | [57] | |
miR-301b | UP | FOXF2 | CL | Cell proliferation and decreasing apoptosis | [59] | |
CML | miR-19b (miR-17-92 cluster) | UP | A20 | AM, BM, CL | Cell proliferation, cell cycle, and decreasing apoptosis | [60] |
miR-328 | DOWN | PIM-1, TCF-4 | CL | Cell proliferation, survival | [61] | |
MDS | miR-378 | DOWN | CDC40 | CL, PS (BM) (N = 20) | Inducing the apoptosis and blocking the cell cycle of MDS cells | [69] |
MM | miR-21 | UP | PTEN, Rho-B, BTG2 | AM, CL | Growth and anti-apoptotic activity | [70] |
miR-221/222 | UP | p27Kip1, PUMA, PTEN, p57Kip2 | AM, CL | Proliferation and cell survival | [71] | |
miR-342-3p | DOWN | FOXQ1 RAP2B CDC42 | CL, PS diagnostic and relapsed MM (N = 93) | Methylation-derived silencing of miR-342-3p might be an early event in MM pathogenesis | [72] | |
miR-140-3p | DOWN | BZW2 | AM, CL | Cell proliferation, decreasing the apoptosis in MM cells | [73] | |
miR-125a-5p | UP | TP53 | CL | Cell proliferation, cell growth decreasing apoptosis of cancer cells | [84] | |
miR-9 | DOWN | FGFR1 CDK6 | CL PS (N = 200) | MiR-9 hypermethylation lead to the activation of oncogenic pathways and represents a prognostic factor for survival | [85] | |
ALL | miR-124a | DOWN | CDK6 | AM, CL, PS (N = 353) | Cell proliferation and growth of ALL cells | [56] |
T-ALL | miR-204 | DOWN | IRAK1, NF-kB | AM, CL, PS (N = 32) | T-ALL growth and metastasis by increased IRAK1 and activation of NF-kB signaling pathway and targets | [74] |
CLL | miR-125a, miR-223 | DOWN | BCL2, STAT3 | PS (N = 30) | Control of white blood cell production | [76] |
miR-22 | UP | PTEN | PS (N = 22) | B-CLL cell proliferation | [86] | |
miR-15a, miR-16-1 | DOWN | DLEU2 | AM, PBMC | Decreasing apoptosis and cell cycle of malignant B-cells | [75] | |
NHL | miR-34a | DOWN | TP53, CDK6 | CL, PS (N = 32) | MiR-34a is preferentially hypermethylated in NHL, the role of miR-34a in lymphomagenesis | [87] |
miR-29 | DOWN | IGF-1R, CDK6 | CL | Cell survival and growth regulation in MCLs | [79] | |
DLBCL | miR-155 | UP | HDAC4 | AM, CL | Block the development of B cells at the immature stage and induce cell proliferation | [78] |
Malignancy | MiRNA | Sample Type | Expression Pattern | No. of Patients | Diagnosis | Prognosis | Therapy Response | Ref. |
---|---|---|---|---|---|---|---|---|
ALL | miR-146a | Plasma | UP | N = 66 | Diagnostic marker pediatric and adult ALL | DOWN after CHT | [99] | |
ALL pediatric | miR-155a | BM | UP | N = 45 | MRD, poor prognosis | DOWN after CHT | [100] | |
miR-155 | BM | UP | N = 42 | Poor outcome | [101] | |||
miR-200c and miR-326 | BM | DOWN | N = 46 | Drug resistance | [102] | |||
miR-324-3p and miR-508-5p | BM | DOWN | N = 50 | Drug resistance | [103] | |||
let-7b, miR-511, and miR-708 miR-196a, miR-383, and miR-542-5p | BM, PB | DOWN UP | N = 81 | Genetic subtype discrimination | [104] | |||
miR-99a, miR-100, and miR-125b | UP | Drug resistance | ||||||
miR-10a, miR-33, miR-134, miR -214, miR -215, miR-369-5p, miR -484, miR-496, miR-518d, miR-572, miR-580, miR-599, miR-624, and miR-627 | UP or DOWN | Clinical outcome | ||||||
miR-151a-5p, miR-151b, miR-195-5p, miR-371b-5p, miR-425-5p, miR-455-5p, miR-497-5p, miR-574-5p, miR-708-5p, and miR-1266-5p | BM, PB | DOWN | N = 16 | T-ALL and B-ALL discrimination | [105] | |||
miR-29c-5p, miR-424-5p, miR-450a-5p miR-450b-5p, miR-542-5p, and miR-629-5p | UP | |||||||
B-ALL pediatric | miR-21 | BM, PB | UP | N = 75 | Shorter DFS and OS | [106] | ||
miR-101-3p, miR-631, miR-922, miR-1324, miR-4699-5p, and miR-4774-5p | BM | UP | N = 40 | Prediction of early relapse | [107] | |||
Precursor B-ALL pediatric | miR-151-5p and mR-451 | BM | DOWN | N = 189 | Shorter RFS | [108] | ||
miR-1290 | UP | |||||||
ALL and AML | miR-128a and miR-128b | BM | UP in ALL | N = 136 | ALL and AML discrimination | [109] | ||
let-7b and miR-223 | DOWN in ALL | |||||||
AML | miR-125b | Exosomes | UP | N = 154 | Higher risk of relapse and overall death | [97] | ||
miR-363 | PB | UP | N = 162 | Shorter EFS and OS | Preference allo-HCST to CHT | [110] | ||
miR-504-3p | Serum | DOWN | N = 134 | Shorter OS | [111] | |||
miR-199b-5p, miR-301b, miR-326, miR-361-5p, miR-625, and miR-655 | Plasma | UP | N = 8 | DOWN after CHT | [112] | |||
AML pediatric | miR-183 | BM, serum | UP | N = 106 | Shorter PFS and OS | [113] | ||
miR-199a | BM | DOWN | N = 71 | Higher BM blasts | Shorter EFS | Lower therapy response | [114] | |
miR-370 | BM, serum | DOWN | N = 106 | Shorter RFS and OS | [115] | |||
miR-146a, miR-509, miR-542, and miR-3667 | unknown | UP | N = 229 * | Shorter OS | [116] | |||
CLL | miR-32-5p, miR-98-5p, and miR-374b-5p | PB | DOWN | N = 32 | Early diagnosis | [117] | ||
B-CLL | miR-145-5p and miR-185-5p | Plasma | DOWN | N = 40 | B-CLL detection | [118] | ||
CML | miR-142-5p | BM, PB | DOWN | N = 45 | Drug resistance | [119] | ||
miR-146a | Plasma | DOWN | N = 60 | Prediction of imatinib response | [120] | |||
miR-150 | Plasma | DOWN | N = 60 | Prediction of imatinib response, UP after CHT | [121] | |||
miR-150 | PB | DOWN | N = 24 | Potential marker for blast crisis and hematologic relapses | [122] | |||
miR-486-5p | PB | DOWN | N = 36 | Early diagnosis | Prediction of imatinib response, UP after CHT | [123] | ||
miR-20, miR-106, and miR-222, | Plasma | UP | N = 50 | Potential markers for therapy response | [124] | |||
miR-122 and miR-126 | PB | DOWN | N = 100 | Prediction of imatinib response, UP after CHT | [125] | |||
DLBCL | miR-99a-5p and miR-125b-5p | Exosomes | UP | Shorter PFS | CHT resistance | [98] | ||
miR-199a and miR-497 | LN biopsies | UP | N = 63 | Longer OS | Drug sensitivity DOWN after CHT | [126] | ||
MM | miR-19a | Serum | DOWN | N = 108 | Shorter PFS and OS | Bortezomib sensitivity | [127] | |
miR-194 | BM | UP | N = 44 | Longer OS | [128] | |||
miR-223-3p | BM | DOWN | N = 94 | Shorter OS | [129] | |||
miR-410 | BM | UP | N = 97 | Shorter PFS and OS | [130] | |||
miR-15a | BM | DOWN | N = 117 | Shorter PFS and OS | [131] | |||
miR-16-1 | MM detection | |||||||
let-7b and miR-18a | Exosomes | DOWN | N = 156 | Shorter PFS and OS | [95] | |||
miR-17 and miR-885-5p | BM | UP | N = 163 | Risk stratification | [132] | |||
miR-720 and miR-1246 | PB | UP | N = 60 | Shorter PFS | [133] | |||
miR-15a-5p, miR-16-5p, miR-17-5p, and miR-20a-5p | Exosomes | DOWN | N = 330 | Bortezomib resistance | [94] | |||
miR-15a, miR-16-1, miR-17, miR-20a, and miR-92-1 | Plasma | UP | N = 85 | Shorter PFS | [134] | |||
miR-153, miR-296, miR-490, miR-455, miR-500, and miR-642 | BM | DOWN | N = 33 | Shorter EFS | [135] | |||
miR-373, miR-548d, miR-554, and miR-888 | UP | |||||||
miR-4254 | Serum, plasma ** | UP | N = 627 ‡ | Potential marker for MM | [136] | |||
miR-92a | Mainly serum ** | UP | N = 1214 ‡‡ | Shorter PFS and OS | [137] | |||
let-7e, miR-15a, miR-16, miR-25, and miR-744 | DOWN |
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Sevcikova, A.; Fridrichova, I.; Nikolaieva, N.; Kalinkova, L.; Omelka, R.; Martiniakova, M.; Ciernikova, S. Clinical Significance of microRNAs in Hematologic Malignancies and Hematopoietic Stem Cell Transplantation. Cancers 2023, 15, 2658. https://doi.org/10.3390/cancers15092658
Sevcikova A, Fridrichova I, Nikolaieva N, Kalinkova L, Omelka R, Martiniakova M, Ciernikova S. Clinical Significance of microRNAs in Hematologic Malignancies and Hematopoietic Stem Cell Transplantation. Cancers. 2023; 15(9):2658. https://doi.org/10.3390/cancers15092658
Chicago/Turabian StyleSevcikova, Aneta, Ivana Fridrichova, Nataliia Nikolaieva, Lenka Kalinkova, Radoslav Omelka, Monika Martiniakova, and Sona Ciernikova. 2023. "Clinical Significance of microRNAs in Hematologic Malignancies and Hematopoietic Stem Cell Transplantation" Cancers 15, no. 9: 2658. https://doi.org/10.3390/cancers15092658
APA StyleSevcikova, A., Fridrichova, I., Nikolaieva, N., Kalinkova, L., Omelka, R., Martiniakova, M., & Ciernikova, S. (2023). Clinical Significance of microRNAs in Hematologic Malignancies and Hematopoietic Stem Cell Transplantation. Cancers, 15(9), 2658. https://doi.org/10.3390/cancers15092658