SET-NUP214 Fusion Gene at Chromosome 9q34 Contributed to the Development of Not Only T-ALL, but Also Primary and Secondary AML.

Abstract 4696

SET-NUP214 rearrangement at chromosome 9q34 is an extremely rare recurrent cryptic deletion resulting from del(9)(q34.11q34.13) mainly found in T-cell acute lymphoblastic leukemia (T-ALL). A multiplex RT-PCR system (HemaVision; DNA Technology) covering 28 leukemic fusion transcripts was applied to 271 bone marrow (BM) samples obtained from acute leukemia patients at initial diagnosis to investigate new pathophysiologic role of SET-NUP214 fusion gene. Out of 271 samples, we identified three cases (1.1%) harboring SET-NUP214 rearrangement – each case of adult T-ALL, pediatric acute myeloid leukemia (AML) from chronic myeloid leukemia (CML) and adult de novo AML with minimal differentiation (M0). Adult T-ALL occurred in 38-year-old man presented with dizziness and hepatomegaly. Conventional cytogenetic study disclosed normal karyotype and existence of SET-NUP214 fusion gene generated by del(9)(q34.11q34.13) was confirmed by RT-PCR, FISH and direct sequencing. Hematological remission was achieved after treatment of induction chemotherapy but during 7 months follow-up, SET-NUP214 fusion gene was steadily detected by RT-PCR. 13-year-old female with AML M0 converted from CML after treatment of imatinib for 2 months was the second case. Leukemic cells showed negative myeloperoxidase (MPO) and sudan-black B (SBB) staining, positive reaction against CD13, CD33, CD117 and MPO monoclonal antibodies by flowcytometry-based immunophenotyping. Major BCR-ABL1 rearrangement and SET-NUP214 fusion genes were simultaneously detected by RT-PCR, FISH and direct sequencing. She died at 38 days after diagnosis during the chemotherapy. The fusion protein contributed to the leukemogenesis by promoting expression of HOXA cluster genes. Last case was a de novo AML M0 in 39-year-old male. Cytochemical stains of leukemic cells on MPO and SBB were negative and immunophenotyping studies were positive for CD34, HLA-DR, CD13 and CD33. SET-NUP214 rearrangement was detected by multiplex RT-PCR. After treatment of induction and consolidation chemotherapy, he received allogeneous sibling stem cell transplantation (SCT), then complete chimerism was achieved. In clonclusion, SET-NUP214 rearrangement is associated with the development of not only T-ALL, but also primary and secondary AML via aberrant expression of HOXA cluster genes.