1. ASXL1mutations in AML are associated with specific clinical and cytogenetic characteristics
- Author
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Aggeliki Daraki, Fotios Panitsas, Chara Giatra, Ioanna Vlachadami, Agapi Ioannidou, Maria Pagoni, Theodoros Marinakis, Kalliopi N. Manola, Diamantina Vasilatou, Katerina Kakosaiou, Constantina Sambani, Paraskevi Apostolou, and Vassiliki Pappa
- Subjects
Adult ,Male ,0301 basic medicine ,Cancer Research ,Adolescent ,Carcinogenesis ,Leukocytosis ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Humans ,Medicine ,Aged ,Chromosome Aberrations ,business.industry ,Age Factors ,Myeloid leukemia ,Neoplasms, Second Primary ,Hematology ,Middle Aged ,Repressor Proteins ,Leukemia, Myeloid, Acute ,030104 developmental biology ,Oncology ,Case-Control Studies ,Myelodysplastic Syndromes ,030220 oncology & carcinogenesis ,Mutation ,Cancer research ,Female ,business - Abstract
Mutations of ASXL1 are early events in acute myeloid leukemia (AML) leukemogenesis and have been associated with unfavorable prognosis. In this study, we investigated the type and frequency of ASXL1 mutations in a large cohort of patients with de novo or secondary AML (s-AML) and looked for correlations with cytogenetic findings and disease features. ASXL1 mutations were associated with older age, s-AML and higher peripheral leukocytosis. We observed more frequent co-occurrence of ASXL1 mutations with trisomy 8 and chromosome 11 aberrations but a negative correlation with myelodysplastic syndromes (MDS)-related cytogenetic abnormalities, especially -5/del(5q) and -7/del(7q). ASXL1 mutations were also found in other genetically defined AML subgroups such as those with t(9;22), inv(3)/t(3;3), t(8;21) or t(15;17); however, none of our inv(16) cases carried ASXL1 mutations. We detected two previously unreported ASXL1 mutations, p.IIe593Val and p.Cys688Tyr. Our findings suggest that ASXL1 mutations tend to cluster with specific clinical and cytogenetic profiles of AML patients.
- Published
- 2018