Resistance to anti-CD19/CD3 BiTE in acute lymphoblastic leukemia may be mediated by disrupted CD19 membrane trafficking
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Resistance to anti-CD19/CD3 BiTE in acute lymphoblastic leukemia may be mediated by disrupted CD19 membrane trafficking. / Braig, Friederike; Brandt, Anna; Goebeler, Mariele; Tony, Hans-Peter; Kurze, Anna-Katharina; Nollau, Peter; Bumm, Thomas; Böttcher, Sebastian; Bargou, Ralf C; Binder, Mascha.
in: BLOOD, Jahrgang 129, Nr. 1, 05.01.2017, S. 100-104.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Resistance to anti-CD19/CD3 BiTE in acute lymphoblastic leukemia may be mediated by disrupted CD19 membrane trafficking
AU - Braig, Friederike
AU - Brandt, Anna
AU - Goebeler, Mariele
AU - Tony, Hans-Peter
AU - Kurze, Anna-Katharina
AU - Nollau, Peter
AU - Bumm, Thomas
AU - Böttcher, Sebastian
AU - Bargou, Ralf C
AU - Binder, Mascha
N1 - Copyright © 2016 American Society of Hematology.
PY - 2017/1/5
Y1 - 2017/1/5
N2 - The CD19 antigen is a promising target for immunotherapy of acute lymphoblastic leukemia (ALL), but CD19-negative relapses remain a major challenge in about 10-20% of patients. Here, we analyzed four CD19-negative ALL relapses after treatment with the CD19/CD3 bispecific T-cell engager blinatumomab. Three were on-drug relapses, with the CD19-negative escape variant first detected after only two treatment courses. In one patient, the CD19-negative clone appeared as a late relapse 19 months after completion of blinatumomab treatment. All four cases showed a cellular phenotype identical to the primary diagnosis except for CD19-negativity. This argued strongly in favor of an isolated molecular event and against a common lymphoid CD19-negative progenitor cell or myeloid lineage shift driving resistance. A thorough molecular workup of one of the cases with early relapse confirmed this hypothesis by revealing a disrupted CD19 membrane export in the post endoplasmic reticulum compartment as molecular basis for blinatumomab resistance.
AB - The CD19 antigen is a promising target for immunotherapy of acute lymphoblastic leukemia (ALL), but CD19-negative relapses remain a major challenge in about 10-20% of patients. Here, we analyzed four CD19-negative ALL relapses after treatment with the CD19/CD3 bispecific T-cell engager blinatumomab. Three were on-drug relapses, with the CD19-negative escape variant first detected after only two treatment courses. In one patient, the CD19-negative clone appeared as a late relapse 19 months after completion of blinatumomab treatment. All four cases showed a cellular phenotype identical to the primary diagnosis except for CD19-negativity. This argued strongly in favor of an isolated molecular event and against a common lymphoid CD19-negative progenitor cell or myeloid lineage shift driving resistance. A thorough molecular workup of one of the cases with early relapse confirmed this hypothesis by revealing a disrupted CD19 membrane export in the post endoplasmic reticulum compartment as molecular basis for blinatumomab resistance.
U2 - 10.1182/blood-2016-05-718395
DO - 10.1182/blood-2016-05-718395
M3 - SCORING: Journal article
C2 - 27784674
VL - 129
SP - 100
EP - 104
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 1
ER -