**5. Conclusion and future directions**

miRNAs are taking place as therapeutic targets promising in the molecular oncology due to their ability to regulate important cellular processes through multiple targets. Their inherent role in carcinogenesis can be as oncogenes or tumor suppressive genes, and the identification of specific biological functions, type of cancer and targets of miRNAs is a critical aspect in the approach of miRNAs therapeutics. Since miRNAs are differentially expressed in distinct stages of lymphopoiesis and influence ALL development, the aberrant miRNAs signatures observed in ALL may be intensively used to determine biomarkers for diagnosis, classification and prognosis. The changes in the expression level of several miRNAs play a functional role in drug resistance, and the reversal of such expression profiles could improve drug sensitivity to obtain better clinical outcomes. The transfection of agomiRs or antagomiRs to miRNAs allows the increase or decrease of specific miRNA expression levels. However, safety concerns and degradation effects limit their efficacy *in vivo*. There is a need for systemic delivery of miRNA as therapeutic agent in the treatment of ALL. The miRNAs listed before represent a low percentage of the total miRNAs studied as potential therapeutic targets. It is quite difficult to present the entire list, nonetheless, there is an available database considered as a valuable source of information for researchers to understand and investigate miRNAs and their targets with diagnostic and therapeutic potential in ALL. Such database is LeukmiR and can be consulted in this link http://tdb.ccmb.res.in/LeukmiR/

**117**

**Author details**

Edgardo Becerra Becerra and Guadalupe García-Alcocer\*

\*Address all correspondence to: leguga@email.com

provided the original work is properly cited.

Unidad de Investigación Genética, Posgrado en Ciencias Químico Biológicas, Facultad de Química, Universidad Autónoma de Querétaro, Querétaro, Mexico

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

*MicroRNAs and Their Role in Acute Lymphoblastic Leukemia*

*DOI: http://dx.doi.org/10.5772/intechopen.94960*

*MicroRNAs and Their Role in Acute Lymphoblastic Leukemia DOI: http://dx.doi.org/10.5772/intechopen.94960*

*Acute Leukemias*

modulated by miR-142-3p, which represses GCR biosynthesis. The inhibition of miR-142-3p in T-ALL cell lines resulted in increased GC-mediated cell death compared to not inhibited cells. Another protein involved in GC resistance via GCR repression is the FKBP51, which is negatively regulated by miR-100 and miR-99. Both miRNAs are found to be downregulated in the T-ALL as well as the B-ALL. In transfected T-ALL cell lines with mimics of miR-100 and miR-99, the result led to enhanced sensitivity to CG and apoptosis. In addition, previous studies reported that miR-100 and miR-99 act synergistically with miR-125 enhancing resistance to VCR [51, 52]. *In vitro* studies indicate that only the overexpression of the three aforementioned miRNAs led to VCR resistance. Moreover, hypoxia is a crucial microenvironmental factor supporting self-renewal of leukemic stem cells in bone marrow niches. miR-210 is one of the hypoxia-regulated miRNAs most studied in cancer including its role in drug resistance and as a prognostic potential. The miR-210 levels were modified in ETV6-RUNX+ Reh and MLL-AF4 + RS4; 11 pediatric ALL cell lines by introducing antagomiR and agomiR to miR-210. After 24 h of the transfection, both cell lines were treated with the DNR, VCR, DEX and L-ASP, individually or in combinations of the four drugs. In ETV6-RUNX+ Reh cells, the half maximal inhibitory concentrations (IC50s) of DNR, DEX and L-ASP were significantly decreased (in agomiR-transfected cells) or increased (in antagomiR-transfected cells) compared to cells transfected with negative control mimics. At the other extreme, the IC50s of DNR, DEX and VCR were decreased (in agomiR-transfected cells) or increased (in antagomiR-transfected cells) in MLL-AF4 + RS4;11 cells [53]. In regards with these findings, the use of agomiRs and antagomiRs to miRNAs could be an alternative to overcome resistance to chemotherapy. Nevertheless, the great challenge in clinical and nonclinical trials, is the

delivery of synthetic miRNAs to leukemia cells effectively.

miRNAs are taking place as therapeutic targets promising in the molecular oncology due to their ability to regulate important cellular processes through multiple targets. Their inherent role in carcinogenesis can be as oncogenes or tumor suppressive genes, and the identification of specific biological functions, type of cancer and targets of miRNAs is a critical aspect in the approach of miRNAs therapeutics. Since miRNAs are differentially expressed in distinct stages of lymphopoiesis and influence ALL development, the aberrant miRNAs signatures observed in ALL may be intensively used to determine biomarkers for diagnosis, classification and prognosis. The changes in the expression level of several miRNAs play a functional role in drug resistance, and the reversal of such expression profiles could improve drug sensitivity to obtain better clinical outcomes. The transfection of agomiRs or antagomiRs to miRNAs allows the increase or decrease of specific miRNA expression levels. However, safety concerns and degradation effects limit their efficacy *in vivo*. There is a need for systemic delivery of miRNA as therapeutic agent in the treatment of ALL. The miRNAs listed before represent a low percentage of the total miRNAs studied as potential therapeutic targets. It is quite difficult to present the entire list, nonetheless, there is an available database considered as a valuable source of information for researchers to understand and investigate miRNAs and their targets with diagnostic and therapeutic potential in ALL. Such database is LeukmiR and can be consulted in this link http://tdb.ccmb.res.in/LeukmiR/

**5. Conclusion and future directions**

**116**
