Cap-Independent Translation in Hematological Malignancies

Abstract

Hematological malignancies are a heterogeneous group of diseases deriving from blood cells progenitors. Although many genes involved in blood cancers contain internal ribosome entry sites (IRESes), there has been only few studies focusing on the role of cap-independent translation in leukemia and lymphomas. Expression of IRES trans-acting factors can also be altered, and interestingly, BCL-ABL1 fusion protein expressed from "Philadelphia" chromosome, found in some types of leukemia, regulates several of them. A mechanism involving c-Myc IRES and cap-independent translation and leading to resistance to chemotherapy in multiple myeloma emphasize the contribution of cap-independent translation in blood cancers and the need for more work to be done to clarify the roles of known IRESes in pathology and response to chemotherapeutics.

Keywords: IRES; cap-independent; leukemia; lymphoma; myeloma; translation.

Figure 1

Schematic summarizing some of the genes and pathways known to influence c-Myc cap-independent translation in multiple myeloma (MM). Cytokine activation of key signaling pathways, or pathway dysregulation, may affect the levels or activity of IRES trans-activating factors (ITAFs), including YB1 (conditions of low Akt activity). MNK1-mediated phosphorylation of hnRNPA1 and/or RPS25 increases interaction between them and might improve ribosome loading on the c-Myc IRES (77). Conventional treatments for MM usually inhibit CAP-dependent translation but their impact on CAP-independent translation is unknown. BMSC, bone marrow stromal cell.