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CD36 defines CML cells less sensitive to imatinib
patient, with the highest CD36 expression after three months of TKI treatment, was subsequently the only one of the three patients that failed to achieve major molecular response (MMR) after 12 months of treatment, a definition of optimal response, according to the 2013 European LeukemiaNet Guidelines (Online Supplementary Table S1).3
CD36 targeting antibodies induce specific killing of CML cells
Having found that CD36 marks cells that are less sensi- tive to imatinib treatment, we next explored CD36 as a potential target for an antibody-based therapy. To this end, we generated a polyclonal antibody targeting CD36. In
Figure 5, Polyclonal antibodies targeting CD36 induce specific killing of CML cells. (A) The CML cell line KU812 with high CD36 expression can be specifically killed by a polyclonal rabbit anti-CD36 antibody in a dose-dependent manner by ADCC when incubated with human NK cells. (B) Primary CD34+ CML cells can be specifically killed by a polyclonal rabbit anti-CD36 antibody in a dose-depen- dent manner by ADCC. The mean of three CML samples is shown; error bars depict standard deviation. (C) NBM samples from healthy donors show a minute ADCC-induced cell death only at the highest tested concentration of antibody. The mean of two NBM samples is shown; error bars depict standard deviation. CML: chronic myeloid leukemia. ADCC: antibody-dependent cellular cytotoxicity; NBM: normal bone marrow.
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Figure 4. CD36 expression is reduced after TKI treatment. (A) BM aspirates from three CML patients treated with imatinib, bosutinib or dasatinib for three months showed a substantial reduction of CD36 expression in the CD34+CD38low compartment as compared to diagnosis. (B) FISH for BCR/ABL1 content on sorted CD34+CD38lowCD36+ and CD34+CD38lowCD36– cells from patient #11 after 3 months imatinib treatment show a higher BCR/ABL1 con- tent in CD36 expressing cells. (C) FISH showing a BCR/ABL1 positive (upper panel) and negative (lower panel) cell. CML: chronic myeloid leukemia.