High expression of the stem cell marker GPR56 at diagnosis identifies acute myeloid leukemia patients at higher relapse risk after allogeneic stem cell transplantation with the CD34 +/CD38 - population

摘要

In patients with acute myeloid leukemia (AML), leukemia-initiating cells (LIC) are believed to be responsible for disease initiation, maintenance, and relapse. While the highest frequency of LIC exists in the CD34+/CD38– bone marrow (BM) compartment,1 over the past years it has become evident that a subset of the CD34– and/or CD38+ population may also harbor AML stem cell potential.2,3 LIC phenotypes also show interindividual heterogeneity dependent on genetic subtypes,4 and new potential LIC markers might better define this population. The G protein-coupled adhesion molecule GPR56 regulates survival, migration, and adhesion in various cell types.5 GPR56 was shown to be upregulated in healthy hematopoietic stem cells as well as LIC, especially when residing in a quiescent state, and to be downregulated during hematopoietic maturation.6 In AML, GPR56 may be important for the LIC - stem cell niche interaction.7 With the ability to serially transplant leukemia in NOD/SCID mice, high GPR56 expressing AML cells were functionally validated as LIC.8,9 This ability was also found in LIC with low or absent CD34 expression, supporting GPR56 as a marker able to identify LIC independent of the CD34 expression status.