CD302 predicts achievement of deep molecular response in chronic myeloid leukemia patients treated with imatinib

Achieving a deep molecular response (DMR) is a prerequisite for treatment-free remission in chronic myeloid leukemia (CML), and a key milestone for CML patients. This study identified patients unlikely to achieve a 5-year DMR through differential expression of cluster of differentiation (CD) genes, and clinical variables at diagnosis. Peripheral blood samples (n=131) from patients treated with imatinib or nilotinib underwent transcriptomic microarray profiling. The decision-tree analysis delineated two distinct poor-risk (PR) cohorts, distinguished by high 3-month BCR::ABL1% (PR-1), or high CD302 expression (PR-2). The 5-years DMR achievement rate was significantly lower in both PR groups compared to the good-risk (GR) group in patients treated frontline with imatinib (0% vs. 27% vs. 83%, p<0.0001), or nilotinib (PR-2 vs GR, 17% vs 83%, p=0.02). Gene-set enrichment analysis revealed reduced expression of cell cycle-related genes in PR-2, as well as increased metabolism and STAT3 pathway genes, which has previously been linked to leukemic cell persistence and resistance to tyrosine kinase inhibitors. Moreover, PR-2 had a higher frequency of CD34+CD302+ and CD14+CD302+ cells compared to GR samples. Strategies aimed at targeting STAT3, and/or metabolic pathways associated with high CD302 may provide novel therapeutic approaches that could help improve treatment outcomes and eradicate residual disease.