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

Lok Lam Ngai, Connie Y. Ma, Orla Maguire, An D. Do, Alberto Robert, Aaron C. Logan, Elizabeth A. Griffiths, Michael J. Nemeth, Cherie Green, Tony Pourmohamad, Bo J. van Kuijk, Alexander N. Snel, Zinia W. Kwidama, Bianca Venniker-Punt, James Cooper, Markus G. Manz, Bjørn T. Gjertsen, Linda Smit, Gert J. Ossenkoppele, Jeroen J.W.M. JanssenJacqueline Cloos, Teiko Sumiyoshi*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)343-353
Number of pages11
JournalEuropean Journal of Haematology
Volume107
Issue number3
DOIs
Publication statusPublished - Sep 2021

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