2. Integrated Genetics (Labcorp), 2000 Vivigen Way, Santa Fe, NM. 87505, USA.
3. Department of Medicine, Division of Hematology and Oncology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Platelet derived growth factor receptor alpha (PDGFRα) undergoes different types of rearrangements creating fusion genes in myeloid neoplasms. Cryptic deletion at 4q12 creating FIP1L1/PDGFRα fusion is the most frequent and is associated with hypereosinophilia. The other infrequent but recurrent abnormality involving PDGFRα seen in myeloid neoplasms is a t(4;12)(q12;p13), which creates a fusion gene with ETV6 and activates ETV6 via the tyrosine kinase domain of the PDGFRα. We characterized a new t(4;12;6) translocation which developed during transformation to acute myeloid leukemia (AML) in a patient with chronic myelomonocytic leukemia (CMML). Standard G-band karyotype analysis and fluorescence in-situ hybridization study (FISH) analysis with a tricolor 4q12 probe and ETV6 was performed on the bone marrow (BM) involved by AML. The karyotype showed a t(4;12;6)( q12;p13;p21.3). FISH showed fusion between PDGFRα and ETV6. Patient did not respond to treatment with imatinib or to standard induction chemotherapy for AML, and expired 11 months from diagnosis. This is the first report of a variant t(4;12;6) and ETV6/PDGFRα fusion that developed during transition from CMML to AML and did not respond to imatinib.
Keywords: CMML, transformed AML, ETV6/PDGFRα fusion