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Bimodal expression of potential drug target CLL-1 (CLEC12A) on CD34+ blasts of AML patients.
- Source :
-
European journal of haematology [Eur J Haematol] 2021 Sep; Vol. 107 (3), pp. 343-353. Date of Electronic Publication: 2021 Jun 26. - Publication Year :
- 2021
-
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.<br />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.<br />Results: The frequency of a bimodal pattern of CLL-1 expression of CD34 <superscript>+</superscript> 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 <superscript>-</superscript> subpopulation may consist of pre-B cells, immature myeloblasts, and hematopoietic stem cells. Furthermore, (pre)-leukemic mutations were detected in both CLL-1 <superscript>+</superscript> and CLL-1 <superscript>-</superscript> subfractions of bimodal samples (N = 3).<br />Conclusions: C-lectin-like molecule 1 bimodality occurs in about 25% of AML patients and the CLL-1 <superscript>-</superscript> cell population still contains malignant cells, hence it may potentially limit the effectiveness of CLL-1-targeted therapies and warrant further investigation.<br /> (© 2021 Genentech Inc. European Journal of Haematology published by John Wiley & Sons Ltd.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1600-0609
- Volume :
- 107
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- European journal of haematology
- Publication Type :
- Academic Journal
- Accession number :
- 34053123
- Full Text :
- https://doi.org/10.1111/ejh.13672