Transcriptome Analysis of Monozygotic Twin Brothers with Childhood Primary Myelofibrosis
- Author:
Ding NAN
1
;
Zhang ZHAOJUN
;
Yang WENYU
;
Ren LAN
;
Zhang YINGCHI
;
Zhang JINGLIAO
;
Li ZHANQI
Author Information
1. CAS Key Laboratory of Genome Sciences and Information
- Keywords:
Primary myelofibrosis;
RNA-seq;
Apoptosis;
Monozygotic twin;
Childhood;
Hematological disease
- From:
Genomics, Proteomics & Bioinformatics
2017;15(1):37-48
- CountryChina
- Language:Chinese
-
Abstract:
Primary myelofibrosis (PMF) is a chronic myeloproliferative disorder in human bonemarrow. Over 50% of patients with myelofibrosis have mutations in JAK2, MPL, or CALR. However,these mutations are rarely detected in children, suggesting a difference in the pathogenesis ofchildhood PMF. In this study, we investigated the response to drug treatment of a monozygotic twinpair with typical childhood PMF. The twin exhibited different clinical outcomes despite following the same treatment regimen. The transcriptomic profiles of patient samples after drug treatment (E2and Y2) were significantly different between the twin pair, which is consistent with the observationthat the drug treatment was effective only in the younger brother, despite the twin being geneticallyidentical. Bioinformatics analysis of the drug-responsive genes showed that the JAK-STAT pathwaywas activated in the cured younger brother, which is opposite to the pathway inhibitionobserved in adult PMF cases following treatment. Moreover, apoptosis and cell cycle processes wereboth significantly influenced by drug treatment in the sample of younger brother (Y2), implyingtheir potential association with the pathogenesis of childhood PMF. Gene mutations in JAK2,MPL, or CALR were not observed; however, mutations in genes including SRSF2 and SF3B1occurred in this twin pair with childhood PMF. Gene fusion events were extensively screened inthe twin pair samples and the occurrence of IGLV2-14-IGLL5 gene fusion was confirmed. The currentstudy reported at transcriptomic level the different responses of monozygotic twin brothers withchildhood PMF to the same androgen/prednisone treatment regimen providing new insights into thepotential pathogenesis of childhood PMF for further research and clinical applications.
