A Leukemic Stem Cell Signature-Based Scoring System for Predicting Prognosis in Myelodysplastic Syndrome Patients

Abstract Leukemic stem cells (LSCs) possess biological properties shared with normal hematopoietic stem cells. They are responsible for chemoresistance and relapse in acute myeloid leukemia (AML). Although myelodysplastic syndrome (MDS) has traditionally been regarded as a “hematopoietic stem cell disorder”, the clinical and biological impact of LSCs on MDS patients are not well defined. To address this question, we used the Affymetrix HTA 2.0 microarray platform to profile 16 out of the 17 recently reported stemness genes (one of them, the ARHGAP22 gene was not included in our array) in our 160 adult primary MDS patients. The diagnoses were based on the 2016 World Health Organization (WHO) classification. Patients with antecedent chemotherapy or hematologic malignancies were excluded. Forty-one (25.6%) patients had MDS with single lineage dysplasia (MDS-SLD), 20 (12.5%) had MDS with ring sideroblasts (MDS-RS), 31 (19.4%) had MDS with multilineage dysplasia (MDS-MLD), 32 (20%) had MDS with excess blasts-1 (MDS-EB1) and 36 (22.5%), MDS-EB2. The risk distribution of the cohort was very-high risk, 15.3%; high risk, 21.3%; intermediate risk, 24.7%; low risk 34.7%; and very-low risk 4% according to the revised international prognosis scoring system (IPSS-R). We identified 4 genes (LAPTM4B, NGFRAP1, NYNRIN, and EMP1) whose expression levels were significantly correlated with overall survival (OS). An LSC4 score (0.731 x LAPTM4B - 1.259 x NGFRAP1 + 0.304 x NYNRIN + 0.231 x EMP1) was constructed based on the weighted sums derived from Cox regression analysis. Higher LSC4 scores were associated with higher IPSS-R scores, complex cytogenetics, and higher incidences of mutations of RUNX1, ASXL1, TP53, SRSF2 and ZRSR2. High-score patients had significantly higher 3-year AML transformation rate (36.3% vs 11.3%, P Download : Download high-res image (802KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.