# Association between leukemic immunophenotype and overall survival in patients with acute promyelocytic leukemia: a retrospective cohort study

**Authors:** Xuan Zha, Li Ma, Yun Yue, XiaoYu Wei, Baolan Sun, Weiguo Wang

PMC · DOI: 10.3389/fcell.2026.1747649 · Frontiers in Cell and Developmental Biology · 2026-01-14

## TL;DR

This study finds that specific immune markers in acute promyelocytic leukemia patients are linked to survival outcomes, with CD2 and CD200 being particularly strong indicators of poor prognosis.

## Contribution

The study identifies CD2 and CD200 as independent adverse prognostic factors for overall survival in APL patients.

## Key findings

- APL blasts show distinct immunophenotypic profiles compared to non-APL AML, with higher CD33 and lower CD7 expression.
- CD2 and CD200 expression are independent adverse prognostic factors for overall survival in APL patients.
- The negative impact of CD2 and CD200 on survival is consistent across patient subgroups.

## Abstract

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) with unique clinical features. Flow cytometry (FCM) immunophenotyping analysis is crucial for accurate diagnosis and prognostic stratification. This study aims to explore the association between specific immune phenotype markers in APL patients and overall survival (OS).

In this retrospective cohort study, immunophenotypic data from 72 APL patients were analyzed by FCM. Continuous and categorical variables are presented as mean ± standard deviation and frequency (percentage), respectively. Group comparisons were performed using ANOVA and Chi-square tests. Cox proportional hazards models were used to identify prognostic factors for OS, with results expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). Kaplan-Meier survival analysis was employed to assess the impact of CD56, CD2, CD34, and CD200 expression on OS. Subgroup analyses were conducted based on age, gender, white blood cell count (WBC), and disseminated intravascular coagulation (DIC).

The baseline age (p = 0.513) and gender (p = 0.881) were comparable across different PML-RARα isoform groups. Compared to non-APL AML, APL blasts were characterized by significantly higher expression of CD33, CD13, CD9, and MPO (all p < 0.05), and lower expression of CD7, CD34, CD56, CD38, CD200, and HLA-DR (all p < 0.001). The PML-RARα (S-type) group showed relatively higher expression of CD34, CD2, and CD200 than the L-type group. Univariate Cox analysis revealed that expression of CD34, CD2, CD56, and CD200 were all significantly associated with poorer OS. After multivariate adjustment, CD2 (adjusted HR = 1.04, 95% CI: 1.01–1.07, p = 0.004) and CD200 (adjusted HR = 1.04, 95% CI: 1.01–1.06, p = 0.009) remained independent adverse prognostic factors. Subgroup analysis confirmed that the negative prognostic impact of CD2 and CD200 expression was consistent across different patient subgroups.

Compared with non-APL-AML patients, APL patients (PML-RARα (S-type) and PML-RARα (L-type)) exhibit unique immunophenotypic changes. The expression frequencies of CD56, CD2, CD34, and CD200 in leukemia cells are significantly correlated with the OS of APL patients, and the high expression of these indicators before treatment may be an adverse prognostic factor for APL patients.

## Linked entities

- **Proteins:** NCAM1 (neural cell adhesion molecule 1), CD2 (CD2 molecule), CD34 (CD34 molecule), CD200 (CD200 molecule), CD33 (CD33 molecule), ANPEP (alanyl aminopeptidase, membrane), CD9 (CD9 molecule), MPO (myeloperoxidase), CD7 (CD7 molecule), CD38 (CD38 molecule)
- **Diseases:** acute promyelocytic leukemia (MONDO:0012883), acute myeloid leukemia (MONDO:0015667), disseminated intravascular coagulation (MONDO:0001243)

## Full-text entities

- **Genes:** MPO (myeloperoxidase) [NCBI Gene 4353], CD34 (CD34 molecule) [NCBI Gene 947], CD7 (CD7 molecule) [NCBI Gene 924] {aka GP40, LEU-9, TP41, Tp40}, CD38 (CD38 molecule) [NCBI Gene 952] {aka ADPRC 1, ADPRC1, cADPR1}, CD2 (CD2 molecule) [NCBI Gene 914] {aka LFA-2, SRBC, T11}, CD33 (CD33 molecule) [NCBI Gene 945] {aka CD33rSiglec, SIGLEC-3, SIGLEC3, p67}, CD9 (CD9 molecule) [NCBI Gene 928] {aka BTCC-1, DRAP-27, MIC3, MRP-1, TSPAN-29, TSPAN29}, ANPEP (alanyl aminopeptidase, membrane) [NCBI Gene 290] {aka AP-M, AP-N, APN, CD13, GP150, LAP1}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, CD200 (CD200 molecule) [NCBI Gene 4345] {aka MOX1, MOX2, MRC, OX-2}
- **Diseases:** AML (MESH:D015470), APL (MESH:D015473), DIC (MESH:D004211), leukemia (MESH:D007938)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

38 references — full list in the complete paper: https://tomesphere.com/paper/PMC12846937/full.md

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Source: https://tomesphere.com/paper/PMC12846937