MIR-29B EXPRESSION IN BREAST TUMORS MIGHT INDUCE ACUTE MYELOID LEUKEMIA THROUGH TET GENE-TARGETING.

BORZONE, FRANCISCO RAÚL; DUCA, ROCÍO BELÉN; FARRÉ, PAULA LUCIA; CHASSEING, NORMA ALEJANDRA; DE SIERVI, ADRIANA; PICCIONI, FLAVIA

CABA

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2020

Sociedad Argentina de Investigación Clínica

Acute Myeloid Leukemia (AML) is a hematopoietic malignancy that can arise as a secondary cancer after breast cancer (BrCa) therapy with alkylating agents or radiotherapy. This type of AML has usually poor prognosis and is refractory. MicroRNAs (miRNAs) are small non-coding RNAs that target mRNA to reduce protein expression. It was reported that miR-125b, -29b, -29c, -101, and -7 are overexpressed in the bone marrow (BM) from AML-patients.Ten-Eleven-Translocation (TET) family genes, including TET1, TET2 and TET3, codify for DNA demethylation enzymes. Particularly, TET2 is a tumor suppressor frequently mutated in AML, and its expression can be controlled by miRNAs. Our aim was to identify TET target miRNAs released by breast tumors and their impact on AML.We evaluated the incidence of BrCa in patients who later developed hematopoietic disorders. Through cBioportal software we found that 5.3% of the patients with leukemia and myelodysplastic syndromes (n=13/292) had developed BrCa previously. Then we analyzed miRNAs expression in breast primary tumors (BPT) or normal adjacent tissue (NAT) from patients obtained from the TCGA Breast Cancer cohort using UCSC Xena resource (n=1,229). Among the five miRNAs overexpressed in AML, only miR-29b was differentially expressed in BPT vs. NAT (p