The role of microRNAs in the biology of B cell leukemias and lymphomas (miRNA in CLL)
- Project Identification
- Project Period
- 7/2014 - 12/2016
- Investor / Pogramme / Project type
- South-Moravian Region
- MU Faculty or unit
- Central European Institute of Technology
The biology of mature B cell malignancies is largely influenced by (i) (dys)-regulation of BCR signaling, and (ii) other microenvironment interactions in the lymphatic tissue. Factors that potentially could regulate BCR signaling and microenvironmental interactions are miRNAs. The miRNAs that regulate essential pathways in immune cells generally are abundantly expressed and evolutionarily conserved. I hypothesize that miRNAs might contribute to the regulation of the activated phenotype of B cells and heterogeneity in B cell receptor (BCR) signaling propensity. This study will focus on a prototype B cell malignancy, namely chronic lymphocytic leukemia (CLL). Two strategies can be used to identify miRNAs involved in microenvironmental interactions: (i) the abundance of miRNA expression seems to be an important determinant of its functionality (ii) miRNAs that are up-/down-regulated after stimulation of their BCR and/or adhesion are likely involved in the regulation of these processes. The primary candidates fulfilling such criteria in CLL include miR-150, miR-29, miR-155, miR-142, and miR-146.
We identified the most abundant miRNA in CLL to be miR-150, which we found expressed at different levels between the CLL cells of patients with differences in their relative proclivity for disease progression. We examined for genes that are differentially expressed between CLL cells that have relatively high versus low levels of miR-150, allowing us to discover the potential regulatory activity of miR-150 on two genes (GAB1 and FOXP1) that may modulate the intensity of BCR-signaling. I plan to study how this miRNA and its targets contribute to the BCR signalling in CLL and other B cell malignancies (specific aim 1), and to study other miRNAs that are potentially involved in BCR signaling (specific aim 2). Our results support the concept that miRNAs have important functions in regulating BCR pathway and microenvironmental interactions in CLL and other B cell malignancies.
Total number of publications: 14