Work

Acute myeloid leukemia with t(4;12)(q12;p13): an aggressive disease with frequent involvement of PDGFRA and ETV6

Year: 2017

Type: article

Abstract: // Jingyi Li 1, 2, * , Jie Xu 1, * , Lynne V. Abruzzo 1, 3 , Guilin Tang 1 , Shaoying Li 1 , M. James You 1 , Gary Lu 1, 4 , Elias J. Jabbour 5 , Qi Deng 2 , Carlos E. Bueso-Ramos 1 , L. Jeffrey Medeiros 1 and C. Cameron Yin 1 1 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 2 Department of Hematology, Tianjin First Center Hospital, Tianjin, China 3 Current address: Department of Pathology, The Ohio State University, College of Medicine, Columbus, OH, USA 4 Current address: Department of Biomedical Sciences, University of South Carolina School of Medicine, Greenville, SC, USA 5 Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA * These authors contributed equally to this work Correspondence to: C. Cameron Yin, email: [email protected] Keywords: acute myeloid leukemia; t(4;12)(q12;p13); PDGFRA; ETV6 Received: September 21, 2017 Accepted: October 13, 2017 Published: December 15, 2017 ABSTRACT We describe the clinical, morphologic, immunophenotypic and molecular genetic features of 15 cases of acute myeloid leukemia (AML) with t(4;12)(q12;p13). There were 9 men and 6 women, with a median age of 50 years (range, 17–76). Most patients had hypercellular bone marrow with a median blast count of 58% and multilineage dysplasia. Flow cytometry analysis showed myeloid lineage with blasts positive for CD13, CD33, CD34, CD38, CD117 and HLA-DR. Interestingly, aberrant CD7 expression was detected in 12/14 cases, and myeloperoxidase was either negative (3/15) or positive in only a small subset of the blasts (12/15). t(4;12)(q12;p13) was detected at time of initial diagnosis in 4 and at relapse or progression in 9 patients. The initial karyotype was unknown in 2 cases. FISH analysis showed PDGFRA-ETV6 rearrangement in all 7 cases assessed. FLT3 ITD was detected in 2/11 cases and IDH2 and JAK2 mutation were each detected in 1/2 cases assessed. There were no mutations of KRAS (0/8), NRAS (0/8), CEBPA (0/3), KIT (0/3), NPM1 (0/3) or IDH1 (0/2). All patients received aggressive multiagent chemotherapy; 7 patients additionally received stem cell transplantation. With a median follow-up of 10 months (range, 6–51), 13 patients died of AML, 1 patient had persistent disease, and 1 patient was lost to follow-up. In summary, AML with t(4;12)(q12;p13) is usually associated with myelodysplasia, aberrant CD7 expression, weak of absent myeloperoxidase expression, frequent PDGFRA-ETV6 fusion, and an aggressive clinical course. The molecular findings suggest that there may be a role for tyrosine kinase inhibitors in patient management.

Source: Oncotarget

DOI: 10.18632/oncotarget.23743