期刊
HAEMATOLOGICA
卷 92, 期 2, 页码 163-169出版社
FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.10980
关键词
GPIAP1; GIT2; PRKG2; PDGFRB; imatinib
类别
资金
- 'Deutsche Jose Carreras Leukamie-Stiftung e.V.', Germany [DJCLS R06/02]
- Competence Network Acute and chronic leukemias - German Bundesministerium fur Bildung und Forschung (Projekttrager Gesundheitsforschung
- DLR e V.), Germany [01GI9980/6]
- Leukaemia Research Fund, UK
- European LeukemiaNet within the 6th European Community Framework Programme for Research and Technological Development
Background and Objectives We sought to identify new fusion genes with involvement of the platelet-derived growth factor receptor beta gene (PDGFRB) in three patients presenting with various subtypes of chronic myeloproliferative disorders associated with chromosomal aberrations involving chromosome bands 5q31-33. Design and Methods We performed 5' rapid amplification of cDNA ends (5'-RACE)-polymerase chain reaction (PCR) with RNA/cDNA derived from a patient (case #1) with a t(5;12)(q31-33;q24) and a second patient (case #2) with a complex rearrangement involving chromosomes 1, 5 and 11. A newly developed DNA-based 'long-distance inverse PCR' (LDI-PCR) was performed on a third patient (case #3) with a t(4;5;5)(q23;q31;q33). Results In cases #1 and #2, we identified mRNA fusions between GIT2 exon 12 and GPIAP1 exon 7, respectively, and PDGFRB exon 11. In case #3, LDI-PCR revealed a fusion between PRKG2 exon 5 and a truncated PDGFRB exon 12. The region encoding the catalytic domain of PDGFR beta is retained in all three cases, with the partner contributing a coiled-coil domain (GPIAP1, PRKG2) or an ankyrin protein interaction motif (GIT2) that may potentially lead to dimerization and constitutive activation of the fusion proteins. Treatment with imatinib (400 mg/day) has led to sustained complete hematologic remission in all three patients. Interpretation and Conclusions These data provide further evidence that numerous partner genes fuse to PDGFRB in BCR-ABL negative chronic myeloproliferative disorders. Although these fusion genes occur rarely, their identification is essential in order to detect patients in whom targeted treatment with tyrosine kinase inhibitors is likely to be successful.
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