**Abstract**

Post-transcriptional regulation is an important step of gene expression that allows to fine-tune the cellular protein profile (so called proteome) according to the current demands. That mechanism has been developed to aid survival under stress conditions, however it occurs to be hijacked by cancer cells. Adjustment of the protein profile remodels signaling in cancer cells to adapt to therapeutic treatment, thereby enabling persistence despite unfavorable environment or accumulating mutations. The proteome is shaped at the post-transcriptional level by numerous mechanisms such as alternative splicing, mRNA modifications and triage by RNA binding proteins, change of ribosome composition or signaling, which altogether regulate the translation process. This chapter is an overview of the translation disturbances found in leukemia and their role in development of the disease, with special focus on the possible therapeutic strategies tested in acute leukemia which target elements of those regulatory mechanisms.

**Keywords:** leukemia treatment, therapy resistance, mRNA translation, RNA binding proteins, ribosomal proteins

### **1. Introduction**

Translation is one of the regulatory levels that allows cells to adapt the profile of proteins (the proteome) to the current demand of cellular processes like cell division or environmental signals such as hypoxia. Generally, protein synthesis requires activation of the complex mechanisms that are tightly regulated [1]. Since the protein synthesis is related to cell growth and cell cycle, any disturbances of this process can be a mechanism underlying unregulated cell growth, neoplastic transformation and tumor development.

For the great majority of cellular mRNAs, the 5′ cap-dependent translation is the most efficient mechanism of protein synthesis [2]. An alternative mechanism of translation initiation is engaged during cell cycle progression [3], cell differentiation and apoptosis, as well as during cellular stress response [4]. Global regulation of translation is often based on the activation or inhibition of one or more components of the translational machinery (eukaryotic initiation factors, ribosomal proteins, ribosomal RNA), whereas the specific regulation often occurs through the action of two groups of factors: *cis*-acting elements found in mRNA molecule

(specific mRNA sequences such as internal ribosome entry sites IRES, mRNA posttranscriptional modifications) and *trans*-acting factors (such as RNA-binding proteins, microRNAs) that bind to mRNA [5]. Furthermore, changes in the cellular signaling can also trigger translational reprogramming. Based on the significant role that all steps of the translation regulation play in development of cancers, including hematological malignancies, and their pro-survival and adaptive function, therapeutic targeting of those mechanisms has been proposed and studied.
