ABSTRACT
Ring 21 is an unstable structural abnormality of chromosome 21 that can lead to RUNX1 gene amplification. We present a unique case with a carrier patient of a constitutional ring chromosome 21 (partial monosomy and trisomy 21) with dysmorphic features and congenital malformations phenotype, who developed acute myeloid leukaemia with myelodysplasia-related changes and two ring 21 chromosomes with RUNX1 amplification. The patient's constitutional ring 21 chromosome showed alterations in tumour suppressor genes, and oncogenes, but not in RUNX1. RUNX1 gene expression at acute myeloid leukaemia diagnosis, showed no upregulation, so other genes may also be the genetic amplification targets in this patient. Copyright © 2016 John Wiley & Sons, Ltd.
Subject(s)
Core Binding Factor Alpha 2 Subunit/genetics , Leukemia, Myeloid, Acute/genetics , Myelodysplastic Syndromes/genetics , Child, Preschool , Chromosomes, Human, Pair 21/genetics , Female , Gene Amplification , Humans , Ring ChromosomesABSTRACT
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, GeneticSubject(s)
Common Variable Immunodeficiency/genetics , IgA Deficiency/genetics , IgG Deficiency/genetics , Transmembrane Activator and CAML Interactor Protein/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Alleles , Case-Control Studies , Child , Child, Preschool , Cohort Studies , Female , Genotype , Humans , Immunologic Deficiency Syndromes/genetics , Male , Middle Aged , Mutation , Young AdultABSTRACT
No disponible
