Leukemic transformation driven by an ASXL1 mutation after a JAK2V617F-positive primary myelofibrosis: clonal evolution and hierarchy revealed by next-generation sequencing

Journal of Hematology & Oncology

Vicente Vicente²  Carlos Besses¹  José M Torregrosa²  Eva Caparrós²  Ginés Luengo-Gil²  Pablo Carbonell⁴  Gloria Soler²  Luz Martínez-Avilés³  Beatriz Bellosillo³  Francisca Ferrer-Marín² 

[1] Department of Hematology, Hospital del Mar-IMIM, Barcelona, Spain;Hematology and Medical Oncology Unit, Hospital Universitario Morales-Meseguer, Centro Regional de Hemodonación, C/Ronda de Garay, sn. 3003, Murcia, Spain;Department of Pathology, Hospital del Mar-IMIM, Barcelona, Spain;Molecular Genetics Unit, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain

关键词: Next-generation sequencing;    Clonality;    Acute myeloid leukemia;    Gene mutations;    ASXL1;    Myelofibrosis;   

Others  :  817358
DOI  :  10.1186/1756-8722-6-68

 received in 2013-09-01, accepted in 2013-09-03,  发布年份 2013

【 摘 要 】

We have characterized the molecular changes underlying the transformation of a JAK2V617F⁺-myelofibrosis with trisomy 8, into a JAK2V617F-negative leukemia. Leukemic clone did not carry JAK2V617F mutation, but showed ASXL1 mutation (R693X). This mutation was identified in a low percentage at diagnosis by next-generation sequencing. Using this technology in serial specimens during the follow-up, we observed a progressive expansion of the ASXL1-mutated minor clone, whereas the JAK2V617F⁺-clone carrying trisomy 8 decreased. Hematologic progression occurred simultaneously with an ASXL1-R693X-negative lung-cancer. This is the first report showing a clear association between the expansion of an ASXL1-mutated clone and the leukemic transformation of myelofibrosis.

【 授权许可】

   
2013 Ferrer-Marín et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 2.

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