Deletions of PURA, at 5q31, and PURB, at 7p13, in myelodysplastic syndrome and progression to acute myelogenous leukemia.
Deletions or monosomy of chromosomes 5 and 7 are frequently observed in myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML). In this study two genes, PURA and PURB, encoding functionally cooperative proteins in the Pur family, are localized to chromosome bands 5q31.1 and 7p13, respectively. One or both of these loci are shown to be hemizygously deleted in 60 MDS or AML patients using fluorescence in situ hybridization (FISH). High-resolution mapping of PURA localizes it approximately 1.1 Mb telomeric to the EGR-1 gene. Frequency of PURA deletion and segregation with EGR-1 indicate that PURA is within the most commonly deleted segment in myeloid disorders characterized by del(5)(q31). No mutations have been detected within the coding sequence of PURA. Concurrent deletions of PURA and PURB occur in MDS at a rate nearly 1.5-fold higher than statistically expected and in AML at a rate > 5-fold higher. This novel simultaneous deletion of two closely related gene family members may thus have consequences related to progression to AML. Pur alpha, an Rb-binding protein, has been implicated in cell cycle control and differentiation, and Pur alpha and Pur beta are reported to function as heterodimers. Alterations in these genes could affect a delicate balance critical in myeloid development.
Lezon-Geyda
K
K
Department of Pathology, Biochemistry and Molecular Biology, Derald H Ruttenberg Cancer Center, New York, NY, USA.
Najfeld
V
V
Johnson
E M
EM
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D018450:Disease Progression; D051766:Early Growth Response Protein 1; D005260:Female; D017353:Gene Deletion; D015723:Gene Library; D005838:Genotype; D006801:Humans; D017874:Immediate-Early Proteins; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics; D009419:Nerve Tissue Proteins; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics; D014178:Translocation, Genetic
D017362:Cyclic AMP Response Element-Binding Protein; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C501130:PURA protein, human; C491579:PURB protein, human; C121485:Pura protein, mouse; D014157:Transcription Factors