The level of blast CD33 expression positively impacts the effect of gemtuzumab ozogamicin in patients with acute myeloid leukemia.
نویسندگان
چکیده
Laboratoire d’Hématologie et Unité Mixte de Recherche 7276 Centre National de la Recherche Scientifique, Centre Hospitalier Universitaire (CHU) de Limoges, Faculté de Médecine, Université de Limoges et Centre National de la Recherche Scientifique, Limoges, France; Service d’Hématologie Biologique, CHU, Dijon, France; Service d’Hématologie Biologique, Hôpital Saint Antoine, Assistance Publique–Hôpitaux de Paris (AP-HP), Paris, France; Laboratoire d’Hématologie, CHU, Lille, France; Service d’Hématologie Adulte, Hôpital Saint-Louis, AP-HP, Université Paris Diderot, Paris, France; Service d’Hématologie, CHU, Dijon, France; Service d’Hématologie, Hôtel Dieu, Hôpital Saint Antoine, AP-HP, Paris, France; Centre de Biologie et d’Anatomie Pathologique, Hématologie Cellulaire et Immunophénotypage des hémopathies, CHU de Lyon–Hospices Civils de Lyon, Pierre Bénite, France; Département d’Hématologie et Immunologie Biologiques, Hôpitaux universitaire Henri Mondor, AP-HP, University Paris-Est Créteil, Créteil, France; Laboratoire d’Hématologie, CHU, Caen, France; Service d’Hématologie, Centre Hospitalier Lyon Sud, Pierre-Bénite, France; Service d’Hématologie Clinique, Hôpital Henri Mondor, AP-HP, Créteil, France; Service d’Hématologie, CHU, Caen, France; Service d’Hématologie, CHU, Limoges, France; and Service d’Hématologie-Oncologie, Centre Hospitalier, Versailles, France
منابع مشابه
Treatment of a Child with Refractory Acute Myeloid Leukemia with Humanized Anti-CD33 Monoclonal Antibody: A Case Report and Review of Drug Development
Background: The induction chemotherapy regimen for acute myeloid leukemia has evolved as once induction is completed patients progress through the consolidation phase and achieve remission in 76% of cases. For patients with relapsed or refractory disease, alternative chemotherapy agents are available. Monoclonal antibody therapy with biological agents, such as the immunotoxin gemtuzumab ozog...
متن کاملCD34(+)/CD38(-) stem cells in chronic myeloid leukemia express Siglec-3 (CD33) and are responsive to the CD33-targeting drug gemtuzumab/ozogamicin.
BACKGROUND CD33 is a well-known stem cell target in acute myeloid leukemia. So far, however, little is known about expression of CD33 on leukemic stem cells in chronic leukemias. DESIGN AND METHODS We analyzed expression of CD33 in leukemic progenitors in chronic myeloid leukemia by multi-color flow cytometry and quantitative polymerase chain reaction. In addition, the effects of a CD33-targe...
متن کاملMultidrug-resistance phenotype and clinical responses to gemtuzumab ozogamicin.
Expression of multidrug resistance (MDR) features by acute myeloid leukemia (AML) cells predicts a poor response to many treatments. The MDR phenotype often correlates with expression of P-glycoprotein (Pgp), and Pgp antagonists such as cyclosporine (CSA) have been used as chemosensitizing agents in AML. Gemtuzumab ozogamicin, an immunoconjugate of an anti-CD33 antibody linked to calicheamicin,...
متن کاملInfluence of CD33 expression levels and ITIM-dependent internalization on gemtuzumab ozogamicin-induced cytotoxicity.
Gemtuzumab ozogamicin (GO; Mylotarg), a novel immunoconjugate used for treatment of acute myeloid leukemia (AML), contains the humanized anti-CD33 antibody (hP67.6) as a carrier to facilitate cellular uptake of the toxic calicheamicin-gamma(1) derivative. By use of lentivirus-mediated gene transfer to manipulate CD33 expression in myeloid cell lines that normally lack CD33 (murine 32D cells) or...
متن کاملSimultaneously targeting CD45 significantly increases cytotoxicity of the anti-CD33 immunoconjugate, gemtuzumab ozogamicin, against acute myeloid leukemia (AML) cells and improves survival of mice bearing human AML xenografts.
Targeting CD33 or CD45 is currently exploited for immunotherapy of acute myeloid leukemia (AML). Gemtuzumab ozogamicin (GO), an immunoconjugate of an anti-CD33 antibody that facilitates cellular uptake of a toxic calicheamicin-gamma(1) derivative, induces complete remissions in a subset of patients with AML. We herein tested whether simultaneous targeting of CD45 could improve GO cytotoxicity a...
متن کاملHepatic sinusoidal obstruction after gemtuzumab ozogamicin (Mylotarg) therapy.
Gemtuzumab ozogamicin (Mylotarg) targets leukemia cells expressing the CD33 receptor by means of a monoclonal antibody conjugated to a cytotoxic agent, calicheamicin. Treatment of acute myeloid leukemia (AML) with gemtuzumab ozogamicin may result in liver injury. We reviewed the course of 23 patients who were given gemtuzumab ozogamicin for AML that had relapsed after hematopoietic cell transpl...
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ورودعنوان ژورنال:
- Blood
دوره 127 17 شماره
صفحات -
تاریخ انتشار 2016