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Title: The hypereosinophilic syndrome: fluorescence in situ hybridization detects the del(4)(q12)-FIP1L1/PDGFRA but not genomic rearrangements of other tyrosine kinases
Authors: La Starza, Roberta ×
Specchia, Giorgina
Cuneo, Antonio
Beacci, Donatella
Nozzoli, Chiara
Luciano, Luigiana
Aventin, Anna
Sambani, Constantina
Testoni, Nicoletta
Foppoli, Marco
Invernizzi, Rosangela
Marynen, Peter
Martelli, Massimo F
Mecucci, Christina #
Issue Date: May-2005
Series Title: Haematologica vol:90 issue:5 pages:596-601
Abstract: BACKGROUND AND OBJECTIVES: According to WHO criteria, the idiopathic hypereosinophilic syndrome (HES) is defined as persistent eosinophilia (>1.5x10(9)/L) without underlying causes, which is associated with signs or symptoms of organ involvement. Increased bone marrow blasts (>5%) or cytogenetic/genetic markers indicate chronic eosinophilic leukemia (CEL). A cryptic deletion of 4q12, i.e. del(4)(q12), producing the FIP1L1/PDGFRA fusion gene, identifies a distinct CEL subgroup (4q-/CEL). Our aims were: a) to use interphase-fluorescent in situ hybridization (FISH) to detect the cryptic 4q12 deletion; b) to compare the clinico-hematologic features of 4q-/CEL with other HES; c) to investigate whether PDGFRB, FGFR1, ABL1, and ETV6-activated tyrosine kinases are rearranged in CEL/HES. DESIGN AND METHODS: This multicenter study included 20 patients fulfilling the WHO criteria for HES and 6 patients without signs/symptoms of end-organ involvement. Double-color FISH was applied in all cases to investigate del(4)(q12). Further interphase-FISH assessed whether PDGFRB/5q33, FGFR1/8p11, ABL1/9q34, and ETV6/12p13, undergo rearrangements in HES. RESULTS: Ten of the 26 patients (9 males and 1 female) had a cryptic del(4)(q12)-FIP1L1/PDGFRA which was confirmed by reverse transcription polymerase chain reaction (RT-PCR) analysis in four. Hepatomegaly and splenomegaly were significantly more frequent in these 10 than in the other 16 patients. Seven of these 10 patients received imatinib mesylate therapy and all achieved hematologic remission. In 3 of the patients interphase-FISH and RT-PCR demonstrated cytogenetic and molecular remission. Improvements were observed in signs and symptoms of cardiac and central nervous system involvement in 2 and 1 patient, respectively. Rearrangements of PDGFRB, FGFR1, ABL1, or ETV6 were not detected in this study. INTERPRETATION AND CONCLUSIONS: FISH is a reliable diagnostic test for differentiating 4q-/CEL from other forms of HES, allowing an early diagnosis of good responders to imatinib mesylate therapy. For the first time we show that PDGFRB, FGFR1, ABL1 and ETV6 are not rearranged in HES and 4q-/CEL cases we studied.
URI: 
ISSN: 0390-6078
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Clinical Genetics
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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