The CD33 splice isoform lacking exon 2 as therapeutic target in human acute myeloid leukemia
CD Godwin, GS Laszlo, BL Wood, CE Correnti… - Leukemia, 2020 - nature.com
CD Godwin, GS Laszlo, BL Wood, CE Correnti, OM Bates, EE Garling, ZJ Mao, ME Beddoe…
Leukemia, 2020•nature.comThere is long-standing interest in therapies targeting fulllength CD33 (CD33FL) for acute
myeloid leukemia (AML)[1–3]. Longer survival with gemtuzumab ozogamicin (GO) in some
patients validates this approach but GO does not benefit many patients with CD33+
leukemias [4]. Numerous efforts to develop more effective CD33-directed therapeutics are
therefore ongoing [5]. The immune-dominant epitopes recognized by existing CD33
therapeutics are located within the membrane-distal V-set domain of CD33FL …
myeloid leukemia (AML)[1–3]. Longer survival with gemtuzumab ozogamicin (GO) in some
patients validates this approach but GO does not benefit many patients with CD33+
leukemias [4]. Numerous efforts to develop more effective CD33-directed therapeutics are
therefore ongoing [5]. The immune-dominant epitopes recognized by existing CD33
therapeutics are located within the membrane-distal V-set domain of CD33FL …
There is long-standing interest in therapies targeting fulllength CD33 (CD33FL) for acute myeloid leukemia (AML)[1–3]. Longer survival with gemtuzumab ozogamicin (GO) in some patients validates this approach but GO does not benefit many patients with CD33+ leukemias [4]. Numerous efforts to develop more effective CD33-directed therapeutics are therefore ongoing [5].
The immune-dominant epitopes recognized by existing CD33 therapeutics are located within the membrane-distal V-set domain of CD33FL (Supplementary Fig. 1)[5]. However, alternative splicing of CD33 results in the transcription of several shorter isoforms in AML cells, with one variant missing exon 2 (CD33ΔE2) being of particular interest [6]. CD33 ΔE2 is predicted to contain only the
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