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Biomarkers of Gemtuzumab Ozogamicin Response for Acute Myeloid Leukemia Treatment

Abstract : Gemtuzumab ozogamicin (GO, Mylotarg(R)) consists of a humanized CD33-targeted antibody-drug conjugated to a calicheamicin derivative. Growing evidence of GO efficacy in acute myeloid leukemia (AML), demonstrated by improved outcomes in CD33-positive AML patients across phase I to III clinical trials, led to the Food and Drug Administration (FDA) approval on 1 September 2017 in CD33-positive AML patients aged 2 years and older. Discrepancies in GO recipients outcome have raised significant efforts to characterize biomarkers predictive of GO response and have refined the subset of patients that may strongly benefit from GO. Among them, CD33 expression levels, favorable cytogenetics (t(8;21), inv(16)/t(16;16), t(15;17)) and molecular alterations, such asNPM1,FLT3-internal tandem duplications and other signaling mutations, represent well-known candidates. Additionally, in depth analyses including minimal residual disease monitoring, stemness expression (LSC17 score), mutations or single nucleotide polymorphisms in GO pathway genes (CD33,ABCB1) and molecular-derived scores, such as the recently set up CD33_PGx6_Score, represent promising markers to enhance GO response prediction and improve patient management.
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Soumis le : vendredi 11 mars 2022 - 12:17:36
Dernière modification le : jeudi 1 septembre 2022 - 04:03:21

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Laurene Fenwarth, Elise Fournier, Meyling Cheok, Thomas Boyer, Fanny Gonzales, et al.. Biomarkers of Gemtuzumab Ozogamicin Response for Acute Myeloid Leukemia Treatment. International Journal of Molecular Sciences, MDPI, 2020, 21 (16), ⟨10.3390/ijms21165626⟩. ⟨hal-03605829⟩



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