Comprehensive analysis of genetic factors predicting overall survival in Myelodysplastic syndromes

• Published in: Scientific reports Vol. 12; no. 1; p. 5925
• Main Authors: Maurya, Nehakumari, Mohanty, Purvi, Dhangar, Somprakash, Panchal, Purvi, Jijina, Farah, Mathan, S. Leo Prince, Shanmukhaiah, Chandrakala, Madkaikar, Manisha, Vundinti, Babu Rao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08-04-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67; 692/4028; Cytogenetics; Genetic analysis; Genetic factors; Hematological diseases; High-Throughput Nucleotide Sequencing; Humanities and Social Sciences; Humans; Janus kinase 2; multidisciplinary; Mutation; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - diagnosis; Myelodysplastic Syndromes - genetics; Next-generation sequencing; p53 Protein; Patients; Prognosis; Runx1 protein; Science; Science (multidisciplinary); Survival; Survival Analysis
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-09864-9

Myelodysplastic syndromes (MDS) are a group of clonal hematological disease with high risk of progression to AML. Accurate risk stratification is of importance for the proper management of MDS. Genetic lesions (Cytogenetic and Molecular mutations) are known to help in prognosticating the MDS patients. We have studied 152 MDS patients using cytogenetics and next generation sequencing (NGS). These patients were evaluated and as per cytogenetic prognostic group, majority (92.1%) of the patients classified as good (81.6%) and intermediate (10.5%) group. The NGS identified 38 different gene mutations in our cohort. Among 111 MDS patients with mutations, the most frequent mutated genes were
SF3B1
(25.2%),
SRSF2
(19%)
U2AF1
(14.4%)
ASXL1
(9.9%)
RUNX1
(9.9%)
TET2
(9%),
TP53
(9%),
ATM
(6.3%),
NRAS
(5.4%) and
JAK2/3
(5.4%). The survival analysis revealed that the mutations in
TP53
,
JAK2/3
,
KRAS
,
NRAS
and
ASXL1
were significantly (
P
 < 0.05) associated with poor survival of the patients. The univariate cox and multivariate cox analysis of our study suggested that the age, marrow morphology, cytogenetic and gene mutations with IPSS-R should be considered for prognosticating the MDS patients. We have proposed M-IPSS-R which changed the risk stratification i.e. 66.3% patients had decreased risk whereas 33.75% showed increased risk compared to IPSS-R. The survival analysis also showed that the M-IPSS-R were more significant in separating the patients as per their risk than the IPSS-R alone. The change in risk stratification could help in proper strategy for the treatment planning.