Optimal management of acute myeloid leukemia (AML) requires accurate monitoring of treatment response, but minimal residual disease (MRD) may escape detection. To identify distinctive features of AML cells for universal MRD monitoring, researchers compared genome-wide gene expression of leukemic myeloblasts from patients with AML to that of CD34+ myeloblasts from healthy donors. Aberrantly expressed genes, including some previously associated with “leukemia stem-cells”, were studied by flow cytometry in AML and leukemia-free bone marrow samples. Several were significantly over- or under-expressed in AML, in agreement with gene array results, and some other markers were also expressed at markedly abnormal levels in some AML cases. These markers defined leukemia-associated profiles extending to cells with stem-cell phenotype; markers remained stable during treatment, and at relapse. In 208 samples from 52 patients undergoing chemotherapy, the new markers yielded MRD measurements matching those of standard methods (Spearman r = 0.9816, P <0.0001), and revealed MRD that was otherwise undetectable. The new markers allowed MRD monitoring in consecutive AML patients using the new markers together with contemporary analytical tools, a machine learning algorithm to reduce the high-dimensional datasets. Single leukemic cells among more than 100,000 normal cells could be clearly visualized. This new approach to MRD studies should refine response-adapted treatment for all patients with AML, and provide new eligibility and response criteria for studies of novel agents.
Acute myeloid leukemia (AML), minimal residual disease (MRD), marker
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