FIP1L1-PDGFRA

The fusion protein PDGFRA/FIP1L1 between the platelet-derived growth factor receptor alpha (PDGFRA) gene and the Fip1-like1 (FIP1L1) is identified in 14 to 60% of idiopathic hypereosinophilic syndrome (HES).

It indicates a clonal hypereosinophilic syndrome called F/P-positive chronic eosinophilic leukemia.

Pathology

 FIP1L1-PDGFRA gene fusion by del(4)(q22q22) in

• myeloid proliferations with hyepreosinophilia
  • chronic eosinophilic leukemia(17591942) and idiopathic hypereosinophilic syndrome (MIM.607685) (HES/CEL) (17701174)

• eosinophilia-associated acute myeloid leukemia (17377585)
• lymphoblastic T-cell lymphoma (17377585)

References

 Systemic mastocytosis (SM) associated with chronic eosinophilic leukemia (SM-CEL): detection of FIP1L1/PDGFRalpha, classification by WHO criteria, and response to therapy with imatinib. Florian S, Esterbauer H, Binder T, Müllauer L, Haas OA, Sperr WR, Sillaber C, Valent P. Leuk Res. 2006 Sep;30(9):1201-5. PMID: 16406018

 Vigna E, Lucia E, Gentile M, Mazzone C, Bisconte MG, Gentile C, Armentano A, Ottaviani E, Rondoni M, Martinelli G, Morabito F. PDGFRalpha/FIP1L1-positive chronic eosinophilic leukemia presenting with retro-orbital localization: efficacy of imatinib treatment. Cancer Chemother Pharmacol. 2007 Jun 5; PMID: 17549478

 Metzgeroth G, Walz C, Score J, Siebert R, Schnittger S, Haferlach C, Popp H, Haferlach T, Erben P, Mix J, Müller MC, Beneke H, Müller L, Del Valle F, Aulitzky WE, Wittkowsky G, Schmitz N, Schulte C, Müller-Hermelink K, Hodges E, Whittaker SJ, Diecker F, Döhner H, Schuld P, Hehlmann R, Hochhaus A, Cross NC, Reiter A.Recurrent finding of the FIP1L1-PDGFRA fusion gene in eosinophilia-associated acute myeloid leukemia and lymphoblastic T-cell lymphoma.Leukemia. 2007 Jun;21(6):1183-8. PMID: 17377585

 Sada A, Katayama Y, Yamamoto K, Okuyama S, Nakata H, Shimada H, Oshimi K, Mori M, Matsui T; Japanese Elderly Leukemia and Lymphoma Study Group. A multicenter analysis of the FIP1L1-alphaPDGFR fusion gene in Japanese idiopathic hypereosinophilic syndrome: an aberrant splicing skipping the alphaPDGFR exon 12. Ann Hematol. 2007 Dec;86(12):855-63. PMID: 17701174

 Lambert F, Heimann P, Herens C, Chariot A, Bours V. A case of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia with a rare FIP1L1 breakpoint. J Mol Diagn. 2007 Jul;9(3):414-9.PMID: 17591942

 Cools J, Stover EH, Gilliland DG. Detection of the FIP1L1-PDGFRA fusion in idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia.Methods Mol Med. 2006;125:177-87. PMID: 16502585

 Cools J, Stover EH, Wlodarska I, Marynen P, Gilliland DG. The FIP1L1-PDGFRalpha kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia. Curr Opin Hematol. 2004 Jan;11(1):51-7. PMID: 14676627

 Metzgeroth G, Walz C, Score J, Siebert R, Schnittger S, Haferlach C, Popp H, Haferlach T, Erben P, Mix J, Müller MC, Beneke H, Müller L, Del Valle F, Aulitzky WE, Wittkowsky G, Schmitz N, Schulte C, Müller-Hermelink K, Hodges E, Whittaker SJ, Diecker F, Döhner H, Schuld P, Hehlmann R, Hochhaus A, Cross NC, Reiter A.Recurrent finding of the FIP1L1-PDGFRA fusion gene in eosinophilia-associated acute myeloid leukemia and lymphoblastic T-cell lymphoma.Leukemia. 2007 Jun;21(6):1183-8. PMID: 17377585

 Walz C, Curtis C, Schnittger S, Schultheis B, Metzgeroth G, Schoch C, Lengfelder E, Erben P, Muller MC, Haferlach T, Hochhaus A, Hehlmann R, Cross NC, Reiter A. Transient response to imatinib in a chronic eosinophilic leukemia associated with ins(9;4)(q33;q12q25) and a CDK5RAP2-PDGFRA fusion gene. Genes Chromosomes Cancer. 2006 Oct;45(10):950-6. PMID: 16845659

 Baccarani M, Cilloni D, Rondoni M, et al. The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome: results of a multicenter prospective study. Haematologica 2007;92:1173-1179.

 Cools J, DeAngelo DJ, Gotlib J, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 2003;348:1201-1214.

Imatinib

 Baccarani M, Cilloni D, Rondoni M, et al. The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome: results of a multicenter prospective study. Haematologica 2007;92:1173-1179.

 Cools J, DeAngelo DJ, Gotlib J, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 2003;348:1201-1214.