@article{cb499b00d5b5448987691dedcedc2597,
title = "Bimodal expression of potential drug target CLL-1 (CLEC12A) on CD34+ blasts of AML patients",
abstract = "Objectives: This study aims to retrospectively assess C-lectin-like molecule 1 (CLL-1) bimodal expression on CD34+ blasts in acute myeloid leukemia (AML) patients (total N = 306) and explore potential CLL-1 bimodal associations with leukemia and patient-specific characteristics. Methods: Flow cytometry assays were performed to assess the deeper immunophenotyping of CLL-1 bimodality. Cytogenetic analysis was performed to characterize the gene mutation on CLL-1-negative subpopulation of CLL-1 bimodal AML samples. Results: The frequency of a bimodal pattern of CLL-1 expression of CD34+ blasts ranged from 8% to 65% in the different cohorts. Bimodal CLL-1 expression was most prevalent in patients with MDS-related AML (P =.011), ELN adverse risk (P =.002), NPM1 wild type (WT, P =.049), FLT3 WT (P =.035), and relatively low percentages of leukemia-associated immunophenotypes (P =.006). Additional immunophenotyping analysis revealed the CLL-1− subpopulation may consist of pre-B cells, immature myeloblasts, and hematopoietic stem cells. Furthermore, (pre)-leukemic mutations were detected in both CLL-1+ and CLL-1− subfractions of bimodal samples (N = 3). Conclusions: C-lectin-like molecule 1 bimodality occurs in about 25% of AML patients and the CLL-1− cell population still contains malignant cells, hence it may potentially limit the effectiveness of CLL-1-targeted therapies and warrant further investigation.",
keywords = "CD34 blasts, CLL-1, acute myeloid leukemia, bimodality, bone marrow aspirates, flow cytometry",
author = "Ngai, {Lok Lam} and Ma, {Connie Y.} and Orla Maguire and Do, {An D.} and Alberto Robert and Logan, {Aaron C.} and Griffiths, {Elizabeth A.} and Nemeth, {Michael J.} and Cherie Green and Tony Pourmohamad and {van Kuijk}, {Bo J.} and Snel, {Alexander N.} and Kwidama, {Zinia W.} and Bianca Venniker-Punt and James Cooper and Manz, {Markus G.} and Gjertsen, {Bj{\o}rn T.} and Linda Smit and Ossenkoppele, {Gert J.} and Janssen, {Jeroen J.W.M.} and Jacqueline Cloos and Teiko Sumiyoshi",
note = "Funding Information: We thank the HOVON/SAKK group, the MRD team of the Amsterdam UMC for performing the immunophenotyping and assistance with data analysis. We would like to acknowledge Linda G. Lutgen and Tara L. Cronin from the Hematologic Procurement Shared Resource and the Flow and Image Cytometry Shared Resource at Roswell Park Comprehensive Cancer Center both supported by National Cancer Institute (NCI) grant P30CA016056. Orla Maguire is an ISAC Marylou Ingram Scholar. Funding Information: We thank the HOVON/SAKK group, the MRD team of the Amsterdam UMC for performing the immunophenotyping and assistance with data analysis. We would like to acknowledge Linda G. Lutgen and Tara L. Cronin from the Hematologic Procurement Shared Resource and the Flow and Image Cytometry Shared Resource at Roswell Park Comprehensive Cancer Center both supported by National Cancer Institute (NCI) grant P30CA016056. Orla Maguire is an ISAC Marylou Ingram Scholar. Publisher Copyright: {\textcopyright} 2021 Genentech Inc. European Journal of Haematology published by John Wiley & Sons Ltd. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = sep,
doi = "https://doi.org/10.1111/ejh.13672",
language = "English",
volume = "107",
pages = "343--353",
journal = "European journal of haematology",
issn = "0902-4441",
publisher = "Wiley-Blackwell",
number = "3",
}