**2. MiRNA biogenesis**

The miRNA genes are transcribed by RNA polymerase II (Pol II) in the nucleus, and the primary miRNAs transcripts (pri-miRNAs) contain cap structures as well as poly(A) tails [7, 8]. The pri-miRNA transcript is processed by the microprocessor complex (Drosha/DGCR8), which crops the pri-miRNAs, producing a pre-miRNA

**59**

*miRNAs in Acute Lymphoblastic Leukemia: Diagnosis, Prognosis and Target Therapeutic*

(transcript of about 70 kb) [9–11]. The exportin 5 (XPO5) mediates the export of the pre-miRNAs from the nucleus to the cytoplasm [12–14]. In the cytosol, the pre-miRNA is recognized by Dicer enzyme (RNAse type III), producing a mature **miRNA duplexes** (miRNA:miRNA\*) about 22 nucleotides [10]. The miRNA duplex binds to the RNA-induced silencing complex (RISC) [which is composed by of the transactivation-responsive RNA-binding protein (TRBP) and Argonaute2 (Ago2)] [8, 15]. The mature strand is retained by the Ago2 protein in the RISC complex, who directs the mature mRNA to its mRNA target for posttranscriptional gene silencing,

Lymphopoiesis is a process by which the hematopoietic stem cells (HSCs) differentiate into lymphoid progenitors and finally into B- or T-lymphocytes [18]. In the process of differentiation, the miRNAs play an important role. miR-29a and miR-196b are highly expressed by HSCs, and their downregulation is associated with differentiation into lymphoid progenitors [19, 20]. It has been reported that miR-17, miR-24, miR-155, miR-128, and miR-181 act to prevent the differentiation

miRNA-150 is expressed in both mature B- and T-cells. The lymphoid progeni-

B-cell differentiation is regulated by the miR-155, and it has been observed that miR-155 levels are upregulated rapidly in both activated mature T- and B-cells [24]. Also, miRNA-155 regulates the differentiation of T-cells into Th type 1 cells [24, 25]. miR-181 is specifically expressed in hematopoietic cell, and its expression is dynamically regulated during early hematopoiesis and lineage commitment. miR-181 expression is high in the early B-cell differentiation stage and progressively decreases subsequently, and its ectopic expression in hematopoietic stem/progenitor cells led to an increased fraction of B-lineage cells in both tissue culture differentiation assays and adult mice [26]. Additionally, miR-181 also plays an important

The miRNA-15 family is an element required to promote the switch from pre-B-cell proliferation to a more differentiated stage. [28]. So, pre-B-cells lacking miRNA-15 family functions exhibit prolonged proliferation because of aberrant expression of the target genes cyclin E1 and D3, and they additionally fail to trigger the transcriptional reprogramming normal to their differentiation, resulting in a

Six miRNAs, miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1, and miR-92a-1 are part of the miR-17-92 cluster; these small molecules are important for mature B-cell development. Absence of the cluster leads to the development of disorders in the maturation from pro-B to pre-B stage [29]. Ventura et al. using miR-17-92-deficient mice found that B-cell development is inhibited at the pro-B to pre-B stage differentiation [30]. The above shows that if the miR-17-92 family miRNAs control the pro- to pre-B transition during B-cell development [31]. Likewise, it has been showed that in helper T cells, the miR-17–92a cluster is critical for the differentia-

miR-29b is increased in Th1 cells, and the levels from this miRNA decrease significantly upon T cell activation. So, the miR-29 expression can serve as a regulator

tors express the miRNA-150 to give rise to the mature B-cells and assist in the transition from progenitor B-cell (pro-B) to the precursor B-cell (pre-B) stage [18]. And premature expression of miRNA-150 results in blocked transition from the

while the complementary strand is degraded [16, 17] (**Figure 1**).

**3. Functions of the miRNAs in lymphopoiesis**

pro-B-cell stage to the pre-B-cell stage [22, 23].

developmental block at the pre-B-cell stage [28].

of early-stage progenitors [21].

role in T-cell development [27].

tion from Th1 cells [32].

*DOI: http://dx.doi.org/10.5772/intechopen.84318*

*miRNAs in Acute Lymphoblastic Leukemia: Diagnosis, Prognosis and Target Therapeutic DOI: http://dx.doi.org/10.5772/intechopen.84318*

(transcript of about 70 kb) [9–11]. The exportin 5 (XPO5) mediates the export of the pre-miRNAs from the nucleus to the cytoplasm [12–14]. In the cytosol, the pre-miRNA is recognized by Dicer enzyme (RNAse type III), producing a mature **miRNA duplexes** (miRNA:miRNA\*) about 22 nucleotides [10]. The miRNA duplex binds to the RNA-induced silencing complex (RISC) [which is composed by of the transactivation-responsive RNA-binding protein (TRBP) and Argonaute2 (Ago2)] [8, 15]. The mature strand is retained by the Ago2 protein in the RISC complex, who directs the mature mRNA to its mRNA target for posttranscriptional gene silencing, while the complementary strand is degraded [16, 17] (**Figure 1**).
