NUP98 gene rearrangements and the clonal evolution of chronic myelogenous leukemia

• Published in: Genes chromosomes & cancer Vol. 30; no. 4; pp. 410 - 415
• Main Authors: Ahuja, Harish G., Popplewell, Leslie, Tcheurekdjian, Lucene, Slovak, Marilyn L.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.04.2001
• Subjects: chromosome 11; chromosome 7; Chromosome Breakage - genetics; Chromosomes, Human, Pair 11 - genetics; Chromosomes, Human, Pair 2 - genetics; Clone Cells; Evolution, Molecular; Female; Homeodomain Proteins - genetics; HOXA9 gene; Humans; Karyotyping; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Membrane Proteins - genetics; Middle Aged; myelodysplastic syndrome; Neoplasm Proteins - genetics; Nuclear Pore Complex Proteins; Nuclear Proteins - genetics; NUP98 gene; Oncogene Proteins, Fusion - genetics; Translocation, Genetic
• ISSN: 1045-2257; 1098-2264
• DOI: 10.1002/1098-2264(2001)9999:9999<::AID-GCC1108>3.0.CO;2-9

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. © 2001 Wiley‐Liss, Inc.