Lineage plasticity of leukemic blasts. Importance for detection of minimal residual disease and study of hematopoesis

Acute leukemia is the most common malignancy in children. According to the origin of the leukemic blasts, two types of leukemia are distinguished - lymphoid (ALL) and myeloid (AML). The focus of this thesis is lineage plasticity of the leukemic blasts. In about 2-5% of leukemias, blasts share immunophenotypic features of both lymphoid and myeloid lineages. In international retrospective study we showed superior overall survival in patients treated according to lymphoid type of protocol compared to patients treated to myeloid type of protocol, especially in cases with CD19 positivity on the blasts. Another type of the plasticity and diagnostic uncertainty in leukemia is ALL with early switch to monocytic lineage. About 8% of B cell precursor ALL underwent monocytic switch in our consecutive cohort. This phenomenon is more common among DUX4r, PAX5-P80R and ZNF384r leukemias. Discrepancy between minimal residual disease (MRD) measured by flow cytometry and quantitative assessment of immunoreceptor rearrangements method occurs because of the loss of B-lymphoid markers. We investigated transdifferentiation process by mass cytometry. By the multilabel panel we were able to determine the sequence of changes in proteins and transcription factors by new tviblindi algorithm. Targeted treatment, such as..