Article Publish Status: FREE
Abstract Title:

High stem cell frequency in acute myeloid leukemia at diagnosis predicts high minimal residual disease and poor survival.

Abstract Source:

Clin Cancer Res. 2005 Sep 15 ;11(18):6520-7. PMID: 16166428

Abstract Author(s):

Anna van Rhenen, Nicole Feller, Angèle Kelder, August H Westra, Elwin Rombouts, Sonja Zweegman, Marjolein A van der Pol, Quinten Waisfisz, Gert J Ossenkoppele, Gerrit Jan Schuurhuis

Article Affiliation:

Department of Hematology, VU University Medical Center, Amsterdam, the Netherlands.


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.

Study Type : In Vitro Study

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