ABSTRACT
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.
Subject(s)
DNA-Binding Proteins/genetics , Gene Expression , Homeodomain Proteins/genetics , Leukemia, Myeloid, Acute/etiology , Myeloid Cells/metabolism , Neoplasm Proteins/genetics , Neoplasms, Second Primary , Nuclear Pore Complex Proteins/genetics , Oncogene Proteins, Fusion/genetics , Proto-Oncogenes/genetics , Transcription Factors/genetics , fms-Like Tyrosine Kinase 3/genetics , Adolescent , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease Management , Female , Gene Expression Profiling , Humans , Immunophenotyping , In Situ Hybridization, Fluorescence , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/drug therapy , MDS1 and EVI1 Complex Locus Protein , Myeloid Ecotropic Viral Integration Site 1 Protein , Translocation, GeneticABSTRACT
Prognosis of patients relapsing after stem cell transplantation (SCT) is poor if no further treatment is given. A second SCT is a limited option in these high-risk patients. We retrospectively analyzed the outcomes of second SCT in acute myeloid leukemia, myelodysplastic syndrome, and acute lymphoblastic leukemia after a first SCT. Twenty-five of 30 patients received second allogeneic SCT. Variables related to survival were disease status before second allogeneic SCT and time interval between transplants more than 1 year (P<.01 and P<.02 in multivariate analysis). Treatment-related mortality was 33% with no impact of the conditioning regimen on overall survival. Second allogeneic SCT in selected patients may be an option in this group with a poor outcome.
