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A CIBERSORTx-based immune cell scoring system could independently predict the prognosis of patients with myelodysplastic syndromes
- Source :
- Blood Advances
- Publication Year :
- 2021
-
Abstract
- Key Points CIBERSORTx analytical approach reveals M0, M2, and eosinophil fractions in the BM to be the most relevant prognostic factors in patients with MDS.High-risk immune cell scores correlate with NF-κB signaling, oxidative stress, and leukemic stem cell signature pathways.<br />Visual Abstract<br />Aside from cell intrinsic factors such as genetic alterations, immune dysregulation in the bone marrow (BM) microenvironment plays a role in the development and progression of myelodysplastic syndromes (MDS). However, the prognostic implications of various immune cells in patients with MDS remain unclear. We adopted CIBERSORTx to estimate the relative fractions of 22 subtypes of immune cells in the BM of 316 patients with MDS and correlated the results with clinical outcomes. A lower fraction of unpolarized M0 macrophages and higher fractions of M2 macrophages and eosinophils were significantly associated with inferior survival. An immune cell scoring system (ICSS) was constructed based on the proportion of these 3 immune cells in the BM. The ICSS high-risk patients had higher BM blast counts, higher frequencies of poor-risk cytogenetics, and more NPM1, TP53, and WT1 mutations than intermediate- and low-risk patients. The ICSS could stratify patients with MDS into 3 risk groups with distinct leukemia-free survival and overall survival among the total cohort and in the subgroups of patients with lower and higher disease risk based on the revised International Prognostic Scoring System (IPSS-R). The prognostic significance of ICSS was also validated in another independent cohort. Multivariable analysis revealed that ICSS independently predicted prognosis, regardless of age, IPSS-R, and mutation status. Bioinformatic analysis demonstrated a significant correlation between high-risk ICSS and nuclear factor κB signaling, oxidative stress, and leukemic stem cell signature pathways. Further studies investigating the mechanistic insight into the crosstalk between stem cells and immune cells are warranted.
- Subjects :
- Oncology
medicine.medical_specialty
NPM1
Cell
medicine.disease_cause
Immune system
Bone Marrow
Internal medicine
medicine
Tumor Microenvironment
Humans
Leukemia
Myeloid Neoplasia
business.industry
Myelodysplastic syndromes
Hematology
Immune dysregulation
medicine.disease
Prognosis
medicine.anatomical_structure
International Prognostic Scoring System
Myelodysplastic Syndromes
Cytogenetic Analysis
Bone marrow
Stem cell
business
Nucleophosmin
Subjects
Details
- ISSN :
- 24739537
- Volume :
- 5
- Issue :
- 22
- Database :
- OpenAIRE
- Journal :
- Blood advances
- Accession number :
- edsair.doi.dedup.....5cb5423463b1fc8f126ce9bd45b0b013