# Percentage of CD56+ monocytes at neutrophil engraftment is associated with the incidence of acute graft-versus-host disease

**Authors:** Ken Hashimoto, Takahiko Sato, Yuichi Ishikawa, Yuki Okuhiro, Daisuke Sugiyama, He Zhang, Sachiko Ito, Yuichiro Inagaki, Kotaro Miyao, Masashi Sawa, Takanobu Morishita, Tatsunori Goto, Tetsuya Nishida, Nobuaki Fukushima, Kazutaka Ozeki, Ryo Hanajiri, Seitaro Terakura, Hiroyoshi Nishikawa, Hitoshi Kiyoi

PMC · DOI: 10.1007/s00277-026-06897-2 · Annals of Hematology · 2026-03-02

## TL;DR

A specific type of monocyte, marked by CD56, is linked to the risk of acute graft-versus-host disease after stem cell transplants.

## Contribution

Identifies CD56+ monocytes as a novel predictive biomarker for acute graft-versus-host disease.

## Key findings

- CD56+ monocytes transiently increase at neutrophil engraftment in patients.
- Lower CD56+ monocyte frequency correlates with reduced acute GVHD incidence.
- CD56+ monocytes show pro-inflammatory gene expression patterns.

## Abstract

Acute graft-versus-host disease (GVHD) is one of the serious complications following allogeneic hematopoietic stem cell transplantation (HSCT) that leads to non-relapse mortality. Although several biomarkers for acute GVHD have been proposed, no definitive predictive markers are clinically available. Recent studies have shown that a specific subset of peripheral blood monocytes expresses CD56 (neural cell adhesion molecule [NCAM]), particularly under inflammatory conditions; however, their role in allogeneic HSCT remains unclear. Single-cell RNA sequencing of peripheral blood mononuclear cells from patients with acute GVHD identified a unique monocyte subset characterized by an NCAM signature. Prospective multicolor flow cytometry analysis of peripheral blood samples revealed a transient increase in CD56⁺ monocytes at the time of neutrophil engraftment. Gene set enrichment analysis demonstrated pro-inflammatory transcriptome signatures of the CD56+ monocyte fraction. Notably, a reduced frequency of CD56⁺ monocytes was significantly associated with a lower incidence of acute GVHD, suggesting their potential as novel predictive cellular biomarkers of acute GVHD.

The online version contains supplementary material available at 10.1007/s00277-026-06897-2.

## Linked entities

- **Genes:** NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684]
- **Proteins:** NCAM1 (neural cell adhesion molecule 1)
- **Diseases:** acute graft-versus-host disease (MONDO:0020546)

## Full-text entities

- **Genes:** TNFRSF8 (TNF receptor superfamily member 8) [NCBI Gene 943] {aka CD30, D1S166E, Ki-1}, CCR2 (C-C motif chemokine receptor 2) [NCBI Gene 729230] {aka CC-CKR-2, CCR-2, CCR2A, CCR2B, CD192, CKR2}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, REG3A (regenerating family member 3 alpha) [NCBI Gene 5068] {aka HIP, HIP/PAP, INGAP, PAP, PAP-H, PAP1}, FCGR3A (Fc gamma receptor IIIa) [NCBI Gene 2214] {aka CD16-II, CD16A, FCG3, FCGR3, FCRIIIA, FcGRIIIA}, CD14 (CD14 molecule) [NCBI Gene 929], CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, ITGAM (integrin subunit alpha M) [NCBI Gene 3684] {aka CD11B, CR3A, HNA-4, MAC-1, MAC1A, MO1A}, CD19 (CD19 molecule) [NCBI Gene 930] {aka B4, CVID3}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, CX3CR1 (C-X3-C motif chemokine receptor 1) [NCBI Gene 1524] {aka CCRL1, CMKBRL1, CMKDR1, GPR13, GPRV28, V28}, TNFRSF1A (TNF receptor superfamily member 1A) [NCBI Gene 7132] {aka CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, ALOX5AP (arachidonate 5-lipoxygenase activating protein) [NCBI Gene 241] {aka FLAP}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, ST2 (suppression of tumorigenicity 2) [NCBI Gene 6761], NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, IL2RB (interleukin 2 receptor subunit beta) [NCBI Gene 3560] {aka CD122, IL15RB, IMD63, P70-75}, ITGA6 (integrin subunit alpha 6) [NCBI Gene 3655] {aka CD49f, ITGA6A, ITGA6B, JEB6, VLA-6}
- **Diseases:** leukemia (MESH:D007938), hematological diseases (MESH:D006402), NRM (MESH:D003643), rheumatoid arthritis (MESH:D001172), age-related diseases (MESH:D010024), mixed phenotypeacute leukemia (MESH:D015456), COVID-19 (MESH:D000086382), ALL (MESH:D054198), Crohn's disease (MESH:D003424), inflammatory (MESH:D007249), Acute GVHD (MESH:D006086), Cancer (MESH:D009369), autoimmune diseases (MESH:D001327), acute (MESH:D000208), MDS (MESH:D009190), AML (MESH:D015470)
- **Chemicals:** tacrolimus (MESH:D016559), Ni-L (-), LPS (MESH:D008070), reactive oxygen species (MESH:D017382), MTX (MESH:D008727), cyclophosphamide (MESH:D003520)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12953352/full.md

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Source: https://tomesphere.com/paper/PMC12953352