GSE135028
CD97 is a Critical Regulator of Acute Myeloid Leukemia Stem Cell Function
Despite significant efforts to improve therapies for acute myeloid leukemia (AML), clinical outcomes remain poor. Understanding the mechanisms that regulate the development and maintenance of leukemic stem cells (LSC) is important to reveal new therapeutic opportunities. We have identified CD97, a member of the adhesion class of G-protein coupled receptors (GPCRs), as a frequently upregulated antigen of AML blasts that is a critical regulator of blast function. High levels of CD97 correlate with poor prognosis, and silencing of CD97 reduces disease aggressiveness in vivo. In order to analyze the functional pathways associated with CD97 expression, we generated RNA-sequence data from scrambled shRNA transfected (s-shRNA) and CD97 KD human AML cell line HL60, as well as from MLL-AF9 (MA9) transduced GMPs isolated from CD97-/- and WT mice. These phenotypes are due to CD97's function to promote proliferation, survival, and the maintenance of the undifferentiated state in leukemic blasts. Collectively, our data credential CD97 as a promising therapeutic target on LSCs in AML. Overall design: CD97 knock down (CD97-KD) was performed in the human AML cell line HL60 using lentiviral vectors expressing scramble control sequences (scramble shRNA, s-shRNA) or two shRNAs targeting CD97 (shCD97.1 and shCD97.3). Both shRNAs induced a significant decrease in CD97 mRNA expression. For the MA9 RNA-seq data, we purified HSPCs from wild-type (WT) and CD97 deficient (CD97-/-) mice and transduced them with the leukemogenic oncogene, MLL-AF9 (MA9). We analyzed the transcriptomes of i) scrambled shRNA transduced (s-shRNA) HL60 and CD97 KD HL60, and ii) WT-MA9 and CD97-/--MA9 mouse LSCs (L-GMPs).