Bimodal expression of potential drug target CLL-1 (CLEC12A) on CD34+ blasts of AML patients.
Eur J Haematol
; 107(3): 343-353, 2021 Sep.
Article
em En
| MEDLINE
| ID: mdl-34053123
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Células da Medula Óssea
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Receptores Mitogênicos
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Leucemia Mieloide Aguda
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Biomarcadores Tumorais
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Células Mieloides
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Lectinas Tipo C
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Mutação
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Holanda