NUP98 gene rearrangements and the clonal evolution of chronic myelogenous leukemia.

Abstract	The role of the BCR-ABL fusion gene in the pathogenesis of the chronic phase of chronic myelogenous leukemia (CML) has been well established. Several additional genetic changes have been reported to occur, at varying frequencies, during disease progression to "accelerated" and "blast crisis" phases. The NUP98 gene localized to chromosome band 11p15 has been found at the breakpoints of several distinct chromosomal translocations in patients with both de novo and therapy-related myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML). Using combined cytogenetic and molecular analyses, we have found rearrangements of the NUP98 gene in the leukemic cells of two patients with Philadelphia chromosome-positive CML, during disease evolution. As expected, analysis of the t(7;11)(p15;p15) from one of the patients showed an in-frame NUP98-HOXA9 fusion. The fusion points were similar to previously reported NUP98-HOXA9 fusion points from patients with MDS/AML. Our results indicate that the NUP98 gene is an additional, albeit infrequent, genetic target during clonal evolution of CML.
Authors	H G Ahuja, L Popplewell, L Tcheurekdjian, M L Slovak
Journal	Genes, chromosomes & cancer (Genes Chromosomes Cancer) Vol. 30 Issue 4 Pg. 410-5 (Apr 2001) ISSN: 1045-2257 [Print] United States
PMID	11241795 (Publication Type: Case Reports, Journal Article, Research Support, U.S. Gov't, P.H.S., Review)
Copyright	Copyright 2001 Wiley-Liss, Inc.
Chemical References	Homeodomain Proteins Membrane Proteins Neoplasm Proteins Nuclear Pore Complex Proteins Nuclear Proteins Oncogene Proteins, Fusion homeobox protein HOXA9 nuclear pore complex protein 98
Topics	Chromosome Breakage (genetics) Chromosomes, Human, Pair 11 (genetics) Chromosomes, Human, Pair 2 (genetics) Clone Cells Evolution, Molecular Female Homeodomain Proteins (genetics) Humans Karyotyping Leukemia, Myelogenous, Chronic, BCR-ABL Positive (genetics, pathology) Membrane Proteins (genetics) Middle Aged Neoplasm Proteins (genetics) Nuclear Pore Complex Proteins Nuclear Proteins (genetics) Oncogene Proteins, Fusion (genetics) Translocation, Genetic

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