Niveau: Supérieur, Doctorat, Bac+8
High Stem Cell Frequency in Acute Myeloid Leukemia at Diagnosis Predicts High Minimal Residual Disease and Poor Survival Anna van Rhenen,1 Nicole Feller,1 Ange' le Kelder,1 August H. Westra,1 Elwin Rombouts,2 Sonja Zweegman,1Marjolein A. van der Pol,1 Quinten Waisfisz,1 Gert J. Ossenkoppele,1 and Gerrit Jan Schuurhuis1 Abstract Purpose: In CD34-positive acute myeloid leukemia (AML), the leukemia-initiating event origi- nates from the CD34+CD38 stem cell compartment. Survival of these cells after chemotherapy may lead tominimal residual disease (MRD) and subsequently to relapse.Therefore, theprognos- tic impact of stem cell frequency in CD34-positiveAMLwas 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 com- bined immunodeficientmice directly correlatedwith stem cell frequency of the graft. In patients, a highpercentage of CD34+CD38 stem cells at diagnosis significantly correlatedwith ahighMRD frequency, especially after the third course of chemotherapy. Also, it directly correlated with poor survival.
- cd34
- g12 class
- after chemotherapy
- very high
- showed no
- cd38
- correlation studies
- no significant