Figure 5.

NOX2 expression and activity are higher in patients with FAB M4/M5 acute myeloid leukemia. (A) gp91^phox expression was measured by flow cytometry on the leukemic cells (CD45/SSC gating) present in bone marrow aspirates taken at diagnosis from 74 patients with acute myeloid leukemia (AML). Patients are classified according to the French-American-British classification. The median is represented as a horizontal line for each group. P=0.0057 in one-way analysis of variance (Kruskal-Wallis test) (B) mRNA expression for the CYBB gene was measured by RNA-sequencing in The Cancer Genome Atlas cohort comprising 198 AML patients. (C) gp91^phox surface expression was measured by flow cytometry on AML cells from two patients sorted using CD45/SSC gating and separated according to their level of expression of the CD34 marker. (D) Sorted AML cells (CD34⁺ and CD34^-) for each patient were used to measure production of reactive oxygen species after stimulation with phorbol myristate acetate (PMA) (10 nM). (E) gp91^phox expression (MFI) was measured by flow cytometry on leukemic cells (CD45/SSC gating) present in bone marrow aspirates taken at diagnosis and after the induction chemotherapy (between 15 and 45 days after the beginning of the treatment) from eight AML patients (Online Supplementary Table S3, ID numbers of the patients indicated on the figure). Four of the patients reached complete remission (CR) after induction chemotherapy (16119, 16127, 16185, and 17235), two reached CR after allografting (14056 and 16126) and two never reached CR (17202 and 17217). All patients but one (17235, who was allografted) relapsed. MFI: mean fluorescence intensity, FAB: French-American-British; TCGA: The Cancer Genome Atlas.