Peripheral Blood Profiles Reflecting Progenitor Lineage Balance are Associated With Molecular Response in Chronic...

Early achievement of deep remission improves patients' outcome in chronic myeloid leukemia (CML) treatment, highlighting the need for predictive indicators before therapy initiation. This study aimed to investigate whether baseline hematologic profiles are associated with molecular response in CML. Using hierarchical clustering of complete blood count (CBC) data at diagnosis, patients were stratified into two clusters. Patients in Cluster 1 had higher BCR::ABL1^IS mRNA levels at 3 and 6 months post-treatment and lower rates of major molecular response compared with cluster 2. Cluster 1 also showed increased granulocyte and immature white blood cell counts and decreased erythroid parameters. Flow cytometric analysis of bone marrow mononuclear cells revealed that cluster 1 had a significant increase in hematopoietic stem cell fractions and a higher ratio of granulocyte-macrophage progenitors to megakaryocyte-erythroid progenitors compared with cluster 2. These findings suggest that differences in bone marrow progenitor cell differentiation affect peripheral blood profiles. Artificial intelligence-driven ghost cytometry (GC) comprehensively captured these differences, distinguishing poor responders, with diagnostic GC scores correlating with BCR::ABL1^IS mRNA levels. The study indicates that multivariate analysis of CBC and GC captures biological features associated with early molecular response in CML.