CD34⁺ CD38^- subpopulation without CD123 and CD44 is responsible for LSC and correlated with imbalance of immune cell subsets in AML

Acute myeloid leukemia (AML) is regarded as a stem cell disease. However, no one unique marker is expressed on leukemia stem cells (LSC) but not on leukemic blasts nor normal hematopoietic stem cells (HSC). CD34⁺ CD38- with or without CD123 or CD44 subpopulations are immunophenotypically defined as putative LSC fractions in AML. Nevertheless, markers that can be effectively and simply held responsible for the intrinsical heterogeneity of LSC is still unclear. In the present study, we examined the frequency of three different LSC subtypes (CD34⁺ CD38^-, CD34⁺ CD38^- CD123⁺ , CD34⁺ CD38^- CD44⁺ ) in AML at diagnosis. We then validated their prognostic significance on the relevance of spectral features for diagnostic stratification, immune status, induction therapy response, treatment effect maintenance, and long-term survival. In our findings, high proportions of the above three different LSC subtypes were all significantly characterized with low complete remission (CR) rate, high relapse/refractory rate, poor overall survival (OS), frequent FLT3-ITD mutation, the high level of regulatory T cells (Treg) and monocytic myeloid-derived suppressor cells (M-MDSC). However, there was no significant statistical difference in all kinds of other clinical performance among the three different LSC groups. It was demonstrated that CD34⁺ CD38^- subpopulation without CD123 and CD44 might be held responsible for LSC and correlated with an imbalance of immune cell subsets in AML.