부산대학교 도서관

Introduction Chromosomal rearrangements involving NUP98 gene have been associated with human leukemias such as de novo AML, therapy-related AML (t- AML), myelodysplastic syndrome ( MDS), and chronic myeloid leukemia ( CML). Genetic fusion NUP98- HOXA9, caused by t(7;11)(p15;p15), is a recurrent cytogenetic alteration in de novo acute myeloid leukemia ( AML) usually found in young Asian patients and its description in therapy-related myeloid neoplasms (t- MN) is rare. Only one Asian case with molecular demonstration of the NUP98- HOXA9 fusion has been reported in therapy-related leukemia. NUP98- HOXA9 leukemogenic mechanism is derived from the transcription factor activity of the chimeric protein, which enhances the expression of genes related to cellular differentiation arrest and proliferation. Patients and Methods We studied a Caucasian woman with a therapy-related acute myeloid leukemia after Ewing′s sarcoma. Molecular demonstration of the genetic fusion NUP98- HOXA9 was performed by RT- PCR, and gene expression was analyzed by real-time PCR, including four AML patients with MLL rearrangements for comparative analysis. Cytologic and flow cytometric analysis was also carried out. Results After cytologic and flow cytometric analysis diagnostics was therapy-related myeloid neoplasm (t- MN). The major component of blasts in the acute leukemia was with neutrophilic differentiation, but 13% erythroid lineage blasts were also found. Cytogenetic and FISH analysis revealed t(7;11)(p15;p15) and NUP98- HOXA9 fusion gene was demonstrated. Gene expression analysis showed upregulation of EVI1 and MEIS1 in the index patient, both of them previously related to a worst outcome. Conclusion In this work, we include a detailed molecular, clinical, cytological, and cytometric study of the second t- AML bearing NUP98- HOXA9 genetic fusion. [ABSTRACT FROM AUTHOR]