Mass cytometric functional profiling of acute myeloid leukemia defines cell cycle and immunophenotypic properties that correlate with known responses to therapy
A partir d'échantillons de moelle osseuse prélevés sur 41 patients atteints d'une leucémie myéloïde aiguë et sur 5 témoins sains, cette étude met en évidence l'intérêt de la cytométrie de masse pour rendre compte des réponses thérapeutiques différentes selon les sous-types de la maladie
Acute myeloid leukemia (AML) is characterized by a high relapse rate that has been attributed to the quiescence of leukemia stem cells (LSCs), which renders them resistant to chemotherapy. However, this hypothesis is largely supported by indirect evidence and fails to explain the large differences in relapse rates across AML subtypes. To address this, bone marrow aspirates from 41 AML patients and five healthy donors were analyzed by high-dimensional mass cytometry. All patients displayed immunophenotypic and intracellular signaling abnormalities within CD34+CD38low populations and several karyotype and genotype-specific surface marker patterns were identified. The immunophenotypic stem and early progenitor cell populations from patients with clinically favorable core-binding factor AML demonstrated a five-fold higher fraction of cells in S-phase compared to other AML samples. Conversely, LSCs in less clinically favorable FLT3-ITD AML exhibited dramatic reductions in S-phase fraction. Mass cytometry also allowed direct observation of the in vivo effects of cytotoxic chemotherapy.
Cancer Discovery , résumé, 2015