Stem Cell Programs Are Retained In Human Leukemic Lymphoblasts With Distinct Immunophenotypes

Leukemic lymphoblasts within different immunophenotypic populations possess stem cell Property. It remains largely unknown however whether self-renewal Program is retained from stem cells or endowed to Progenitors by leukemogenic molecules. We have addressed this issue in the context of TEL-AML1-associated acute lymphoblastic leukemia (ALL) by profiling a refined Program edited from genes essential for self-renewal of hematopoietic stem cells and B-cell development. Bioinformatic analysis shows that ALL populations are loosely clustered and all most close to the normal population that contains early lymphoid Progenitors, indicating that immunophenotypes do not reflect maturation stages in ALL and that self-renewal Program might be retained from stem cells. Results of assessing “first hit” function of TEL-AML1 in different populations of normal cells demonstrate the molecular model. Therefore, our studies reveal a leukemogenic scenario of human ALL that programs of stem cells are sustained in distinct fractions by leukemogenic mutations.