RESUMEN
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.
Asunto(s)
Proteínas de Unión al ADN/genética , Expresión Génica , Proteínas de Homeodominio/genética , Leucemia Mieloide Aguda/etiología , Células Mieloides/metabolismo , Proteínas de Neoplasias/genética , Neoplasias Primarias Secundarias , Proteínas de Complejo Poro Nuclear/genética , Proteínas de Fusión Oncogénica/genética , Proto-Oncogenes/genética , Factores de Transcripción/genética , Tirosina Quinasa 3 Similar a fms/genética , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Manejo de la Enfermedad , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunofenotipificación , Hibridación Fluorescente in Situ , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Proteína del Locus del Complejo MDS1 y EV11 , Proteína 1 del Sitio de Integración Viral Ecotrópica Mieloide , Translocación GenéticaRESUMEN
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.
