title: Transcriptome Analysis of Monozygotic Twin Brothers with Childhood Primary Myelofibrosis.
abstract: Primary myelofibrosis (PMF) is a chronic myeloproliferative disorder in human bone marrow. 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 of childhood PMF. In this study, we investigated the response to drug treatment of a monozygotic twin pair 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 (E2 and Y2) were significantly different between the twin pair, which is consistent with the observation that the drug treatment was effective only in the younger brother, despite the twin being genetically identical. Bioinformatics analysis of the drug-responsive genes showed that the JAK-STAT pathway was activated in the cured younger brother, which is opposite to the pathway inhibition observed in adult PMF cases following treatment. Moreover, apoptosis and cell cycle processes were both significantly influenced by drug treatment in the sample of younger brother (Y2), implying their 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 SF3B1 occurred in this twin pair with childhood PMF. Gene fusion events were extensively screened in the twin pair samples and the occurrence of IGLV2-14-IGLL5 gene fusion was confirmed. The current study reported at transcriptomic level the different responses of monozygotic twin brothers with childhood PMF to the same androgen/prednisone treatment regimen providing new insights into the potential pathogenesis of childhood PMF for further research and clinical applications.
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Ding
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Yang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors.forename: Yingchi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors.forename: Jingliao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors.forename: Zhanqi
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors.forename: Peihong
authors.initials: P
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China. Electronic address: chenxj76@163.com.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing 100190, China. Electronic address: fangxd@big.ac.cn.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Fang
mesh_terms: D000728:Androgens / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D002675:Child, Preschool; D002888:Chromosomes, Human, Pair 19; D020732:Cytogenetic Analysis; D020869:Gene Expression Profiling; D050939:Gene Fusion; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D008297:Male; D020125:Mutation, Missense; D010750:Phosphoproteins / Q000235:genetics; D011241:Prednisone / Q000627:therapeutic use; D055728:Primary Myelofibrosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D012313:RNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D000072260:RNA Splicing Factors / Q000235:genetics; D017423:Sequence Analysis, RNA; D000068103:Serine-Arginine Splicing Factors / Q000235:genetics; D014430:Twins, Monozygotic
chemical_list: D000728:Androgens; D007146:Immunoglobulin lambda-Chains; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; C112491:SF3B1 protein, human; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors; D012313:RNA; D011241:Prednisone
keywords: Apoptosis; Childhood; Hematological disease; Monozygotic twin; Primary myelofibrosis; RNA-seq