yoko inaguma

Fusions of the Runt-related transcription factor 1 (RUNX1) with different partner genes have been associated with various hematological disorders. Interestingly, the C-terminally truncated form of RUNX1 and RUNX1 fusion proteins are similarly considered important contributors to leukemogenesis. Here, we describe a 59-year-old male patient who was initially diagnosed with acute myeloid leukemia, inv(16)(p13;q22)/CBFB-MYH11 (FAB classification M4Eo). He achieved complete remission and negative CBFB-MYH11 status with daunorubicin/cytarabine combination chemotherapy but relapsed 3 years later. Cytogenetic analysis of relapsed leukemia cells revealed CBFB-MYH11 negativity and complex chromosomal abnormalities without inv(16)(p13;q22). RNA-seq identified the glutamate receptor, ionotropic, kinase 2 (GRIK2) gene on 6q16 as a novel fusion partner for RUNX1 in this case. Specifically, the fusion of RUNX1 to the GRIK2 antisense strand (RUNX1-GRIK2as) generated multiple missplicing transcripts. Because extremely low levels of wild-type GRIK2 were detected in leukemia cells, RUNX1-GRIK2as was thought to drive the pathogenesis associated with the RUNX1-GRIK2 fusion. The truncated RUNX1 generated from RUNX1-GRIK2as induced the expression of the granulocyte colony-stimulating factor (G-CSF) receptor on 32D myeloid leukemia cells and enhanced proliferation in response to G-CSF. In summary, the RUNX1-GRIK2as fusion emphasizes the importance of aberrantly truncated RUNX1 in leukemogenesis.

A 62 year-old man had recognized annular erythemas on the trunk and limbs which lasted for 2 months. Because a skin biopsy revealed CD8 positive peripheral T-cell lymphoma, he was referred to our hospital. On the initial consultation in our department, annular erythemas and tumors were present on the whole body surface. The abnormal cells were not found in the peripheral blood. Abnormal FDG avid lesions were not found by PET-CT scan, except for the skin. CHOP therapy was started on the initial diagnosis of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). In an additional examination, tumor cells were positive for CD56 and Epstein-Barr virus encoded RNA (EBER) in situ hybridization. The TCR gene rearrangement was negative by Southern blot hybridization method. Therefore the patient was finally diagnosed with primary cutaneous extranodal NK/T cell lymphoma (ENKL). CHOP therapy was not effective ; therefore we switched to SMILE therapy which consists of steroid ; dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide that gave a complete response after 2 courses. Our case showed that differentiation of primary cutaneous ENKL was necessary for the case doubted a CD8-positive PTCL-NOS.[Skin Cancer (Japan) 2014 ; 29 : 258-263]