We studied the CD34+CD38-CD123+ fraction in AML blasts at diagnosis, and its utility as a unique phenotype for minimal residual disease (MRD) of AML patients.
To improve MRD assessment by MFC, we here evaluate the combination of human Myeloid Inhibitory C-type Lectin (hMICL, also termed C-type lectin domain family 12, member A, CLEC12A) and CD 123 (also termed interleukin-3 receptor alpha, IL3RA) in combination with CD34 and CD117 (KIT), as an MRD assay in pre-clinical and clinical testing in 69 AML patients.
The aim of this study was to determine the prognostic power of minimal residual disease (MRD) measured by fluorescence in situ hybridization (FISH) in CD34(+)CD38(-) cells sorted by flow cytometry at different periods during therapy.
This inversely correlates with in vivo CD34+ mobilization and, interestingly, also with the prognosis of the disease: patients showing a good mobilizing activity are resistant to chemotherapy and subject to significantly higher rates of Minimal Residual Disease (MRD) and relapse than the others.
Furthermore, the prognostic relevance of NPM1-based monitoring of minimal residual disease (MRD) in peripheral blood (PB), bone marrow (BM), and in specific cell subsets (CD34(+), CD34(-), CD34(dim)) of BM were evaluated.
Our results indicate that quantitative analysis of CD34 and CD117 may be useful to detect minimal residual disease (MRD) and could be tested in a future to monitor therapy in AML.
Thus, FISH can identify MRD in a majority of t(8;21) patients and, combined with CD34+ selection, may provide an indirect assessment of the differentiation state of residual t(8;21) cells.
Its expression in the majority of human acute leukemias but not in normal mononuclear blood cells and normal CD34+ hematopoietic progenitors qualifies the wt1 gene transcript as a 'pan-acute leukemic' marker probably useful in monitoring minimal residual disease after chemotherapy and in detecting leukemic blast cells in purged or unpurged hematopoietic stem cell preparations intended to be used for autologous bone marrow transplantation.
To prove positive enrichment procedures for the elimination of tumor cells, CD34+ and CD19+ cell fractions obtained from LP samples in an experimental setting via preparative flow cytometry were analyzed for MRD resulting in PCR-negativity for all CD34+ fractions.