1. Bimodal expression of potential drug target CLL-1 (CLEC12A) on CD34+ blasts of AML patients.
- Author
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Ngai LL, Ma CY, Maguire O, Do AD, Robert A, Logan AC, Griffiths EA, Nemeth MJ, Green C, Pourmohamad T, van Kuijk BJ, Snel AN, Kwidama ZW, Venniker-Punt B, Cooper J, Manz MG, Gjertsen BT, Smit L, Ossenkoppele GJ, Janssen JJWM, Cloos J, and Sumiyoshi T
- Subjects
- Antigens, CD34 genetics, Antigens, CD34 immunology, Biomarkers, Tumor immunology, Bone Marrow Cells immunology, Bone Marrow Cells pathology, Cytogenetic Analysis, Female, Flow Cytometry, Gene Expression Profiling, Gene Expression Regulation, Leukemic, Hematopoietic Stem Cells immunology, Hematopoietic Stem Cells metabolism, Hematopoietic Stem Cells pathology, Humans, Immunophenotyping, Lectins, C-Type immunology, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute pathology, Male, Middle Aged, Myeloid Cells immunology, Myeloid Cells pathology, Precursor Cells, B-Lymphoid immunology, Precursor Cells, B-Lymphoid metabolism, Precursor Cells, B-Lymphoid pathology, Primary Cell Culture, Receptors, Mitogen immunology, Biomarkers, Tumor genetics, Bone Marrow Cells metabolism, Lectins, C-Type genetics, Leukemia, Myeloid, Acute genetics, Mutation, Myeloid Cells metabolism, Receptors, Mitogen genetics
- 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., (© 2021 Genentech Inc. European Journal of Haematology published by John Wiley & Sons Ltd.)- Published
- 2021
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