Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia: Involvement of PDGFRB and response to imatinib

Kathryn Wilkinson, Elvira R P Velloso, Luiz Fernando Lopes, Charles Lee, Jon C. Aster, Margaret A. Shipp, Ricardo C T Aguiar

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Eosinophilia is common in myeloproliferative disorders (MPDs) with abnormalities of chromosome band 5q31-33, including those that present with t(1;5)(q23;q33). With the development of rational drug therapy, characterization of the molecular targets for these translocations could guide treatment and affect patient survival. We cloned the t(1;5)(q23;q33) and showed that it fuses platelet-derived growth factor receptor beta (PDGFRB) to the coiled-coil domains of a novel partner protein, myomegalin. Using two-color interphase fluorescence in situ hybridization (FISH), we also demonstrated that the eosinophils are clonal in these disorders. Imatinib mesylate has recently been shown to be efficacious in MPDs with PDGFR activation. Therefore, following our molecular studies, we were able to redirect this patient's treatment. Although she had refractory and progressive disease, once imatinib was started, complete clinical and hematologic remission, as well as major cytogenetic response, was achieved. Given the therapeutic implications, our findings stress the need to aggressively investigate the molecular basis of these diseases, with emphasis on the PDGFR family.

Original languageEnglish (US)
Pages (from-to)4187-4190
Number of pages4
JournalBlood
Volume102
Issue number12
DOIs
StatePublished - Dec 1 2003
Externally publishedYes

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Platelet-Derived Growth Factor beta Receptor
Myeloproliferative Disorders
Cloning
Eosinophilia
Organism Cloning
Patient treatment
Drug therapy
Electric fuses
Chromosomes
Refractory materials
Fluorescence
Chemical activation
Interphase
Color
Fluorescence In Situ Hybridization
Eosinophils
Cytogenetics
Chromosome Aberrations
Therapeutics
Drug Therapy

ASJC Scopus subject areas

  • Hematology

Cite this

Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia : Involvement of PDGFRB and response to imatinib. / Wilkinson, Kathryn; Velloso, Elvira R P; Lopes, Luiz Fernando; Lee, Charles; Aster, Jon C.; Shipp, Margaret A.; Aguiar, Ricardo C T.

In: Blood, Vol. 102, No. 12, 01.12.2003, p. 4187-4190.

Research output: Contribution to journalArticle

Wilkinson, Kathryn ; Velloso, Elvira R P ; Lopes, Luiz Fernando ; Lee, Charles ; Aster, Jon C. ; Shipp, Margaret A. ; Aguiar, Ricardo C T. / Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia : Involvement of PDGFRB and response to imatinib. In: Blood. 2003 ; Vol. 102, No. 12. pp. 4187-4190.
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