Bimodal expression of potential drug target CLL-1 (CLEC12A) on CD34+blasts of AML patients

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.

Automated summary

This study retrospectively assessed C-lectin-like molecule 1 (CLL-1) bimodal expression on CD34+ blasts in acute myeloid leukemia (AML) patients and explored potential CLL-1 bimodal associations with leukemia and patient-specific characteristics. The study found that bimodal CLL-1 expression was most prevalent in patients with MDS-related AML, ELN adverse risk, NPM1 wild type, FLT3 wild type, and relatively low percentages of leukemia-associated immunophenotypes. Additional immunophenotyping analysis revealed that the CLL-1(-) subpopulation may consist of pre-B cells, immature myeloblasts, and hematopoietic stem cells.