A 4-gene leukemic stem cell score can independently predict the prognosis of myelodysplastic syndrome patients
Journal
Blood advances
Date Issued
2020
Author(s)
Abstract
Myelodysplastic syndrome (MDS) comprised a heterogeneous group of diseases. The prognosis of patients varies even in the same risk groups. Searching for novel prognostic markers is warranted. Leukemic stem cells (LSCs) are responsible for chemoresistance and relapse in leukemia. Recently, expressions of 17 genes related to stemness of LSCs were found to be associated with prognosis in acute myeloid leukemia patients. However, the clinical impact of LSC genes expressions in MDS, a disorder arising from hematopoietic stem cells, remains unclear. We analyzed expression profile of the 17 stemness-related genes in primary MDS patients and identified expression of 4 genes (LAPTM4B, NGFRAP1, EMP1, and CPXM1) were significantly correlated with overall survival (OS). We constructed an LSC4 scoring system based on the weighted sums of the expression of 4 genes and explored its clinical implications in MDS patients. Higher LSC4 scores were associated with higher revised International Prognostic Scoring System (IPSS-R) scores, complex cytogenetics, and mutations in RUNX1, ASXL1, and TP53. High-score patients had significantly shorter OS and leukemia-free survival (LFS), which was also confirmed in 2 independent validation cohorts. Subgroup analysis revealed the prognostic significance of LSC4 scores for OS remained valid across IPSS-R lower- and higher-risk groups. Furthermore, higher LSC4 score was an independent adverse risk factor for OS and LFS in multivariate analysis. In summary, LSC4 score can independently predict prognosis in MDS patients irrespective of IPSS-R risks and may be used to guide the treatment of MDS patients, especially lower-risk group in whom usually only supportive treatment is given.
SDGs
Other Subjects
cytarabine; protein p53; transcription factor RUNX1; 4 gene leukemic stem cell score; adult; aged; Article; ASXL1 gene; cancer prognosis; cancer stem cell; chromosome analysis; cohort analysis; controlled study; CPXM1 gene; EMP1 gene; female; gene; gene expression profiling; gene identification; gene mutation; genetic association; hematopoietic stem cell transplantation; human; human cell; International Prognostic Scoring System; LAPTM4B gene; leukemic stem cell; low drug dose; low risk population; major clinical study; male; microarray analysis; myelodysplastic syndrome; NGFRAP1 gene; overall survival; priority journal; prognostic assessment; RUNX1 gene; TP53 gene; validation process