The nature of primitive clonogenic AML cells and the role in emergence of minimal residual disease in AML
01 / 2005 - 04 / 2008
The aim of this study is to identify putative primitive cell populations in AML that give rise to minimal residual disease (MRD) cells and to identify factors that contribute to the escape from the effects of chemotherapeutic treatment. In vitro and in vivo experiments confirmed the stem cell characteristics of the CD34+CD38- population. The amount of stem cells was found to have major impact both on the level of MRD found after chemotherapeutic treatment and patient outcome: a high stem cell frequency, represented by a high percentage of CD34+CD38- cells, predicts high MRD and short survival. Next it was found that the CD34+CD38- cells at diagnosis display expression of the myeloid specific antigen CLL-1, which is not present on normal CD34+CD38- stem cells and which can therefore be used to study minimal residual stem disease after chemotherapy and in addition might be used in future to specifically target the malignant CD34+CD38- population. Next to this antigen expression, other antibody combinations also offer the possibility to perform CD34+CD38- analysis in samples of patient material after treatment, and to quantify malignant cell populations, thereby identifying patients at risk for relapse. Micro-array analysis is being performed on primary patient CD34+CD38- cells to identify stem cell specific characteristics, with a focus on new treatment targets, preferentially those involving production of proliferation stimulatory or inhibitory cytokines and growth factors as well as specific adhesion molecules.