High stem cell frequency in acute myeloid leukemia at diagnosis predicts high minimal residual disease and poor survival
A Van Rhenen, N Feller, A Kelder, AH Westra… - Clinical cancer …, 2005 - AACR
A Van Rhenen, N Feller, A Kelder, AH Westra, E Rombouts, S Zweegman, MA Van Der Pol…
Clinical cancer research, 2005•AACRPurpose: In CD34-positive acute myeloid leukemia (AML), the leukemia-initiating event
originates from the CD34+ CD38− stem cell compartment. Survival of these cells after
chemotherapy may lead to minimal residual disease (MRD) and subsequently to relapse.
Therefore, the prognostic impact of stem cell frequency in CD34-positive AML was
investigated. Experimental Design: First, the leukemogenic potential of unpurified CD34+
CD38− cells, present among other cells, was investigated in vivo using nonobese …
originates from the CD34+ CD38− stem cell compartment. Survival of these cells after
chemotherapy may lead to minimal residual disease (MRD) and subsequently to relapse.
Therefore, the prognostic impact of stem cell frequency in CD34-positive AML was
investigated. Experimental Design: First, the leukemogenic potential of unpurified CD34+
CD38− cells, present among other cells, was investigated in vivo using nonobese …
Abstract
Purpose: In CD34-positive acute myeloid leukemia (AML), the leukemia-initiating event originates from the CD34+CD38− stem cell compartment. Survival of these cells after chemotherapy may lead to minimal residual disease (MRD) and subsequently to relapse. Therefore, the prognostic impact of stem cell frequency in CD34-positive AML was investigated.
Experimental Design: First, the leukemogenic potential of unpurified CD34+CD38− cells, present among other cells, was investigated in vivo using nonobese diabetic/severe combined immunodeficient mice transplantation experiments. Second, we analyzed whether the CD34+CD38− compartment at diagnosis correlates with MRD frequency after chemotherapy and clinical outcome in 92 AML patients.
Results: In vivo data showed that engraftment of AML blasts in nonobese diabetic/severe combined immunodeficient mice directly correlated with stem cell frequency of the graft. In patients, a high percentage of CD34+CD38− stem cells at diagnosis significantly correlated with a high MRD frequency, especially after the third course of chemotherapy. Also, it directly correlated with poor survival. In contrast, total CD34+ percentage showed no such correlations.
Conclusions: Both in vivo data, as well as the correlation studies, show that AML stem cell frequency at diagnosis offers a new prognostic factor. From our data, it is tempting to hypothesize that a large CD34+CD38− population at diagnosis reflects a higher percentage of chemotherapy-resistant cells that will lead to the outgrowth of MRD, thereby affecting clinical outcome. Ultimately, future therapies should be directed toward malignant stem cells.
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