Abstrakt

Identification of the microRNA signature of human CD4 regulatory T lymphocytes in Acute Myeloid Leukemia patients at diagnosis

Hussein Fayyad-Kazan

There is a clear evidence of elevated numbers of CD4 regulatory T lymphocytes (Tregs) in solid and hematological malignancies in addition to possessing an increased suppressive function. This important feature has urged the scientific community to search for ways to interfere with Treg function during or after cancer therapy. But the underlying molecular mechanisms remain largely unknown. Thus, a special focus on microRNA regulation was the goal of our study. In our previous study, we investigated the molecular profile of circulating Tregs in the peripheral blood (PB) of healthy volunteers and identified several miRs differentially expressed between CD4+CD25+CD127low (Tregs) and CD4+CD25- CD127low T cells using the TLDA technique. In fact, a human Treg microRNA signature of AML patients at diagnosis has not been described yet. We thus investigated human CD4+CD25+CD127low Tregs purified from the peripheral blood of AML patients and identified a signature composed of ten differentially expressed miRs (miR-18a, miR-101, miR-133a, miR-135a, miR-302c, miR-324, miR-511, miR-542, miR-618, and miR-758) in comparison to their negative counterpart. Among those miRs, six were upregulated (miR- 18a, miR-101, miR-133a, miR-135a, miR-511, miR-618) whilst four were downregulated (miR-302c, miR-324, miR-542, miR-758). Many potential miRs potential targets were identified in the 3’UTR of genes indispensable for Treg function and are presently under investigation.