# CLL-1: An emerging target for immunotherapy in acute myeloid leukemia

**Authors:** Yu Wang, Yi Xiao

PMC · DOI: 10.1007/s00277-026-06916-2 · Annals of Hematology · 2026-03-14

## TL;DR

This paper reviews CLL-1 as a new target for immunotherapy in acute myeloid leukemia, offering potential for more effective and less toxic treatments.

## Contribution

The paper highlights CLL-1 as a novel immunotherapy target in AML with specific expression in leukemia cells.

## Key findings

- CLL-1 is specifically expressed in AML blast cells and leukemia stem cells.
- Targeting CLL-1 may reduce drug resistance and non-specific toxicity.
- CLL-1-targeted therapies could help overcome immune escape in AML.

## Abstract

AML is an aggressive haematological malignancy characterised by uncontrolled proliferation and differentiation arrest of myeloid progenitor/stem cells. Conventional treatment methods principally entail chemotherapy and haematopoietic stem cell transplantation; however, the efficacy of these treatments is constrained by the occurrence of relapses and treatment-related toxicity. In recent years, research into molecular mechanisms has driven the development of targeted therapies against specific gene mutations and advanced multiple immunotherapy strategies. Among these, C-type lectin-like molecule 1 (CLL-1) has emerged as a promising new immunotherapy target due to its specific expression in AML blast cells and leukemia stem cells. CLL-1-targeted therapies have been shown to have the potential to alleviate drug resistance, reduce non-specific toxicity, and address issues of immune escape. This review provides a comprehensive summary of the latest research advances in CLL-1-targeted therapies for AML, with the aim of providing novel insights and directions for clinical treatment.

## Linked entities

- **Genes:** COLEC10 (collectin subfamily member 10) [NCBI Gene 10584]
- **Diseases:** acute myeloid leukemia (MONDO:0015667), AML (MONDO:0018874)

## Full-text entities

- **Genes:** NCR1 (natural cytotoxicity triggering receptor 1) [NCBI Gene 9437] {aka CD335, LY94, NK-p46, NKP46}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, CXADRP1 (CXADR pseudogene 1) [NCBI Gene 653108] {aka CAR, CXADRP}, CD28 (CD28 molecule) [NCBI Gene 940] {aka IMD123, Tp44}, IL3RA (interleukin 3 receptor subunit alpha) [NCBI Gene 3563] {aka CD123, IL-3R-alpha, IL3R, IL3RAY, IL3RX, IL3RY}, CD33 (CD33 molecule) [NCBI Gene 945] {aka CD33rSiglec, SIGLEC-3, SIGLEC3, p67}, DGAT1 (diacylglycerol O-acyltransferase 1) [NCBI Gene 8694] {aka ARAT, ARGP1, DGAT, DIAR7}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, CXCL1 (C-X-C motif chemokine ligand 1) [NCBI Gene 2919] {aka FSP, GRO1, GROa, MGSA, MGSA-a, NAP-3}, TGFBR2 (transforming growth factor beta receptor 2) [NCBI Gene 7048] {aka AAT3, FAA3, LDS1B, LDS2, LDS2B, MFS2}, CD19 (CD19 molecule) [NCBI Gene 930] {aka B4, CVID3}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, IKBKB (inhibitor of nuclear factor kappa B kinase subunit beta) [NCBI Gene 3551] {aka IKK-2, IKK-beta, IKK2, IKKB, IMD15, IMD15A}, KLRK1 (killer cell lectin like receptor K1) [NCBI Gene 22914] {aka CD314, D12S2489E, KLR, NKG2-D, NKG2D}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, IDH1 (isocitrate dehydrogenase (NADP(+)) 1) [NCBI Gene 3417] {aka HEL-216, HEL-S-26, IDCD, IDH, IDP, IDPC}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, IL15 (interleukin 15) [NCBI Gene 3600] {aka IL-15}, CYBB (cytochrome b-245 beta chain) [NCBI Gene 1536] {aka AMCBX2, CGD, CGDX, GP91-1, GP91-PHOX, GP91PHOX}, SYK (spleen associated tyrosine kinase) [NCBI Gene 6850] {aka IMD82, p72-Syk}, GUSB (glucuronidase beta) [NCBI Gene 2990] {aka BG, MPS7}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, TRAF6 (TNF receptor associated factor 6) [NCBI Gene 7189] {aka MGC:3310, RNF85}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, LAG3 (lymphocyte activating 3) [NCBI Gene 3902] {aka CD223}, HAVCR2 (hepatitis A virus cellular receptor 2) [NCBI Gene 84868] {aka CD366, HAVcr-2, KIM-3, SPTCL, TIM3, TIMD-3}, CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF}, HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, FCGR3A (Fc gamma receptor IIIa) [NCBI Gene 2214] {aka CD16-II, CD16A, FCG3, FCGR3, FCRIIIA, FcGRIIIA}, PDGFRB (platelet derived growth factor receptor beta) [NCBI Gene 5159] {aka CD140B, IBGC4, IMF1, JTK12, KOGS, OPDKD}, CSF3 (colony stimulating factor 3) [NCBI Gene 1440] {aka C17orf33, CSF3OS, GCSF}, LDHA (lactate dehydrogenase A) [NCBI Gene 3939] {aka GSD11, HEL-S-133P, LDHM, PIG19}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, NPM1 (nucleophosmin 1) [NCBI Gene 4869] {aka B23, NPM}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, CISH (cytokine inducible SH2 containing protein) [NCBI Gene 1154] {aka BACTS2, CIS, CIS-1, G18, SOCS}, CD86 (CD86 molecule) [NCBI Gene 942] {aka B7-2, B7.2, B70, BU63, CD28LG2, CD86 v6}, IDH2 (isocitrate dehydrogenase (NADP(+)) 2) [NCBI Gene 3418] {aka D2HGA2, ICD-M, IDH, IDH-2, IDHM, IDP}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, CD3E (CD3 epsilon subunit of T-cell receptor complex) [NCBI Gene 916] {aka CD3epsilon, IMD18, T3E, TCRE}, CD80 (CD80 molecule) [NCBI Gene 941] {aka B7, B7-1, B7.1, BB1, CD28LG, CD28LG1}, PDGFRA (platelet derived growth factor receptor alpha) [NCBI Gene 5156] {aka CD140A, PDGFR-2, PDGFR2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, KLRC1 (killer cell lectin like receptor C1) [NCBI Gene 3821] {aka CD159A, NKG2, NKG2A}, CLEC12A (C-type lectin domain family 12 member A) [NCBI Gene 160364] {aka CD371, CLL-1, CLL1, DCAL-2, MICL, hKLRL1}, IGF1R (insulin like growth factor 1 receptor) [NCBI Gene 3480] {aka CD221, IGFIR, IGFR, JTK13}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, GZMB (granzyme B) [NCBI Gene 3002] {aka C11, CCPI, CGL-1, CGL1, CSP-B, CSPB}, TNFRSF9 (TNF receptor superfamily member 9) [NCBI Gene 3604] {aka 4-1BB, CD137, CDw137, ILA, IMD109}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, CD226 (CD226 molecule) [NCBI Gene 10666] {aka DNAM-1, DNAM1, PTA1, TLiSA1}, CSF1 (colony stimulating factor 1) [NCBI Gene 1435] {aka CSF-1, MCSF, PG-M-CSF}
- **Diseases:** deaths (MESH:D003643), gene (MESH:C537680), -versus-leukemia (MESH:D007938), complement-mediated toxicity (MESH:D020274), AML (MESH:D015470), Myeloid Leukemia (MESH:D007951), infection (MESH:D007239), ICANS (MESH:C000722498), EMDs (MESH:D023981), CRS (MESH:D003398), FAB (OMIM:176500), cytokine release syndrome (MESH:D000080424), cytopenia (MESH:D006402), Neurotoxicity Syndrome (MESH:D020258), prolonged neutropenia (MESH:D008133), Neutropenia (MESH:D009503), bone marrow suppression (MESH:D001855), granulocytopenia (MESH:D000380), Toxicity (MESH:D064420), Myeloproliferative Neoplasm (MESH:D009369), weight loss (MESH:D015431), pancytopenia (MESH:D010198), hypoxia (MESH:D000860), plasma cell tumors (MESH:D010954), hepatic injury (MESH:D056486), APL (MESH:D015473), autoimmune reactions (MESH:D001327), ALL (MESH:D054218), leukaemia (MESH:D015458), inflammation (MESH:D007249), CML (MESH:D015464), B-cell malignancies (MESH:D016393), hematologic malignancies (MESH:D019337), MDS (MESH:D009190), graft-versus-host disease (MESH:D006086)
- **Chemicals:** panobinostat (MESH:D000077767), superoxide (MESH:D013481), CDCA (MESH:D002635), disulfide (MESH:D004220), lactate (MESH:D019344), azacitidine (MESH:D001374), -T (MESH:D014316), ABL602 (-), auristatin (MESH:C543533), calcium (MESH:D002118), PBD (MESH:C438462), nivolumab (MESH:D000077594), lipid (MESH:D008055), Gemtuzumab ozogamicin (MESH:D000079982), glycan (MESH:D011134), tryptophan (MESH:D014364), SN-38 (MESH:D000077146), dolastatin-10 (MESH:C064570), arginine (MESH:D001120), adenosine (MESH:D000241), fludarabine (MESH:C024352), sulfonate (MESH:D000476), amino acid (MESH:D000596), Cy (MESH:D003545), DM4 (MESH:D008453), valine (MESH:D014633), sodium urate (MESH:D014527), ROS (MESH:D017382), cystine (MESH:D003553), PEG-8 (MESH:C000595213), decitabine (MESH:D000077209), citrulline (MESH:D002956), pembrolizumab (MESH:C582435), glucose (MESH:D005947), carbohydrate (MESH:D002241), Blinatumomab (MESH:C510808), cyclophosphamide (MESH:D003520)
- **Species:** Cercopithecidae (monkey, family) [taxon 9527], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** MOLM-13 — Homo sapiens (Human), Adult acute monocytic leukemia, Cancer cell line (CVCL_2119), OCI-AML2 — Homo sapiens (Human), Adult acute myeloid leukemia, Cancer cell line (CVCL_1619), HL-60 — Homo sapiens (Human), Adult acute myeloid leukemia with maturation, Cancer cell line (CVCL_0002)

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12988970