Acute Myeloid Leukemia |
1 Division of Hematology and Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, USA
2 Division of Hematology-Oncology, Chang Gung Memorial Hospital, Taipei, Taiwan
3 School of Medicine, Chang Gung University, Taoyuan, Taiwan
4 Department of Hematology and Oncology
5 the 21st century COE program, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
6 Department of Medical Informatics and Biomathematics, University of Munster, Munster, Germany
7 Pathology/Laboratory Medicine and Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
8 Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan
9 Department of Hematology
10 Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
Correspondence: Tadayuki Akagi, Department of Stem Cell Biology, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan. E-mail:tadayuki{at}staff.kanazawa-u.ac.jp. Sören Lehmann, Department of Hematology M54, Karolinska University Hospital, Huddinge, Stockholm 141 86, Sweden. E-mail:soren.lehmann{at}ki.se.
Translocation of chromosomes 8 and 21, t(8;21), resulting in the AML1-ETO fusion gene, is associated with acute myeloid leukemia. We searched for additional genomic abnormalities in this acute myeloid leukemia subtype by performing single nucleotide polymorphism genomic arrays (SNP-chip) analysis on 48 newly diagnosed cases. Thirty-two patients (67%) had a normal genome by SNP-chip analysis (Group A), and 16 patients (33%) had one or more genomic abnormalities including copy number changes or copy number neutral loss of heterozygosity (Group B). Two samples had copy number neutral loss of heterozygosity on chromosome 6p including the PIM1 gene; and one of these cases had E135K mutation of Pim1. Interestingly, 38% of Group B and only 13% of Group A samples had a KIT-D816 mutation, suggesting that genomic alterations are often associated with a KIT-D816 mutation. Importantly, prognostic analysis revealed that overall survival and event-free survival of individuals in Group B were significantly worse than those in Group A.
Key words: t(8;21), AML1-ETO, CNN-LOH, SNP-chip, KIT, PIM1.