Significance of hematopoietic surface antigen CD34 in neuroblastoma prognosis and the genetic landscape of CD34-expressing neuroblastoma CSCs.
Cell Biol Toxicol
; 37(3): 461-478, 2021 06.
Article
en En
| MEDLINE
| ID: mdl-32979173
ABSTRACT
High-risk neuroblastoma (HR-NB) is branded with hematogenous metastasis, relapses, and dismal long-term survival. Intensification of consolidation therapy with tandem/triple autologous stem cell (SC) rescue (with bone marrow [BM]/peripheral blood [PB] CD34+ selection) after myeloablative chemotherapy has improved long-term survival. However, the benefit is limited by the indication of NB cells in CD34+ PBSCs, CD34 expression in NB cells, and the risk of reinfusing NB cancer stem cells (NB CSCs) that could lead to post-transplant relapse. We investigated the association of CD34 surface expression (92 patients) with NB evolution/clinical outcomes. CD34 gene-level status in NB was assessed through RNA-Seq data mining (18 cohorts, n, 3324). Genetic landscape of CD34-expressing NB CSCs (CD133+CD34+) was compared with CD34- CSCs (CD133+CD34-). RNA-seq data revealed equivocal association patterns of CD34 expression with patient survival. Our immunohistochemistry data revealed definite, but rare (mean, 0.73%; range 0.00-7.87%; median, 0.20%) CD34 positivity in NB. CD34+ significantly associated with MYCN amplification (p, 0.003), advanced disease stage (p, 0.016), and progressive disease (PD, p < 0.0009) after clinical therapy. A general high-is-worse tendency was observed in patients with relapsed disease. High CD34+ correlated with poor survival in patients with N-MYC-amplified HR-NB. Gene expression analysis of CD34+-NB CSCs identified significant up (4631) and downmodulation (4678) of genes compared with NB CSCs that lack CD34. IPA recognized the modulation of crucial signaling elements (EMT, stemness maintenance, differentiation, inflammation, clonal expansion, drug resistance, metastasis) that orchestrate NB disease evolution in CD34+ CSCs compared with CD34- CSCs. While the function of CD34 in NB evolution requires further in-depth investigation, careful consideration should be exercised for autologous stem cell rescue with CD34+ selection in NB patients. Graphical abstract.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Antígenos CD34
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Antígeno AC133
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Proteína Proto-Oncogénica N-Myc
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Antígenos de Superficie
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Neuroblastoma
Tipo de estudio:
Prognostic_studies
Límite:
Child, preschool
/
Female
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Humans
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Infant
/
Male
Idioma:
En
Revista:
Cell Biol Toxicol
Asunto de la revista:
TOXICOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos