Eosinophilia is defined as a peripheral blood eosinophil count > 0.5x10⁹/L, with > 1.5x10⁹/L of eosinophil count sometimes referred to as hypereosinophlia. Eosinophilia is a common clinical phenotype associated with various conditions including allergies, infections, medications, autoimmune disorders and malignancies. Although malignancy-related eosinophilia is rare, it is an important clinical sign of these tumors, which require early diagnosis and clinical intervention. Figure 1 summaries the initial workup of patients with eosinophilia. , (2) Myeloid/lymphoid neoplasms with PDGFRB rearrangement
 , (3) Myeloid/lymphoid neoplasms with FGFR1 rearrangement
 , (4) Provisional entity: Myeloid/lymphoid neoplasms with PCM1/JAK2

WHO 2016 defines a group of myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1 / JAK2 as:

(1) Myeloid/lymphoid neoplasms with PDGFRA rearrangement

This group of patients can be treated with tyrosine kinase inhibitors. While patients with PDGFRA or PDGFRB rearrangement are highly sensitive to Imatinib, PCM1-JAK2 patients had varying responses to JAK2 inhibitor Ruxolitinib, which can induce complete remission, although the duration is often limited. FGFR1 inhibitors have not been very successful in treating tumors with FGFR1 rearrangement. PKC412 was effective in a patient with progressive myeloproliferative disorder with (8;13) (Chen et al., 2004); however, subsequent studies with the FGFR1 inhibitor ponatinib were less successful. Novel FGFR1 inhibitors are currently being tested in clinical trials for solid tumors with FGFR1 activation. Recently a new FGFR family kinase inhibitor INCB054828 induced complete resolution of eosinophilia as well as complete hematologic, cytogenetic and molecular remission in a patient with FGFR1 rearranged MPN (Verstovsek et al., 2018).

The fusion partner genes for PDGFRA, PDGFRB, or FGFR1 have been steadily accumulating and are updated below in Tables.
Table 1: PDGFRA fusion partners, chromosome locations, detection methods and references

Gene name	Rearrangements	Detection methods					References (PMID)
		Karyotype	FISH	RT-PCR		NGS
Genes Involved and Proteins Article Bibliography Pubmed ID Last Year Title Authors 9373237 1997 Fusion of the platelet-derived growth factor receptor beta to a novel gene CEV14 in acute myelogenous leukemia after clonal evolution. Abe A et al 15609342 2005 8p11 myeloproliferative syndrome with a novel t(7;8) translocation leading to fusion of the FGFR1 and TIF1 genes. Belloni E et al 31353276 2019 An aging population of patients with cystic fibrosis undergoes lung transplantation: An analysis of the ISHLT Thoracic Transplant Registry. Benden C et al 28509585 2017 Identification of a novel fusion TBL1XR1-PDGFRB in a patient with acute myeloid leukemia harboring the DEK-NUP214 fusion and clinical response to dasatinib. Campregher PV et al 25658984 2015 Comprehensive genomic profiling identifies a novel TNKS2-PDGFRA fusion that defines a myeloid neoplasm with eosinophilia that responded dramatically to imatinib therapy. Chalmers ZR et al 15448205 2004 PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder. Chen J et al 21938754 2012 Systematic screen for tyrosine kinase rearrangements identifies a novel C6orf204-PDGFRB fusion in a patient with recurrent T-ALL and an associated myeloproliferative neoplasm. Chmielecki J et al 12660384 2003 A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. Cools J et al 17555450 2007 Two novel imatinib-responsive PDGFRA fusion genes in chronic eosinophilic leukaemia. Curtis CE et al 11739186 2001 The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins. Demiroglu A et al 20107158 2010 Screening for diverse PDGFRA or PDGFRB fusion genes is facilitated by generic quantitative reverse transcriptase polymerase chain reaction analysis. Erben P et al 18262053 2008 Fusion of PRKG2 and SPTBN1 to the platelet-derived growth factor receptor beta gene (PDGFRB) in imatinib-responsive atypical myeloproliferative disorders. Gallagher G et al 23041776 2013 A translocation t(2;8)(q12;p11) fuses FGFR1 to a novel partner gene, RANBP2/NUP358, in a myeloproliferative/myelodysplastic neoplasm. Gervais C et al 29169164 2017 A Novel PCM1-PDGFRB Fusion in a Patient with a Chronic Myeloproliferative Neoplasm and an ins(8;5). Ghazzawi M et al 8168137 1994 Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Golub TR et al 17690697 2008 A PDGFRB-positive acute myeloid malignancy with a new t(5;12)(q33;p13.3) involving the ERC1 gene. Gorello P et al 24772479 2014 Identification and functional characterization of imatinib-sensitive DTD1-PDGFRB and CCDC88C-PDGFRB fusion genes in eosinophilia-associated myeloid/lymphoid neoplasms. Gosenca D et al 15034873 2004 Identification of a novel gene, FGFR1OP2, fused to FGFR1 in 8p11 myeloproliferative syndrome. Grand EK et al 15492236 2004 p53-Binding protein 1 is fused to the platelet-derived growth factor receptor beta in a patient with a t(5;15)(q33;q22) and an imatinib-responsive eosinophilic myeloproliferative disorder. Grand FH et al 10688839 2000 FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33). Guasch G et al 12393597 2003 Endogenous retroviral sequence is fused to FGFR1 kinase in the 8p12 stem-cell myeloproliferative disorder with t(8;19)(p12;q13.3). Guasch G et al 28552906 2017 Novel PDGFRB fusions in childhood B- and T-acute lymphoblastic leukemia. Heilmann AM et al 18205209 2008 The t(1;9)(p34;q34) and t(8;12)(p11;q15) fuse pre-mRNA processing proteins SFPQ (PSF) and CPSF6 to ABL and FGFR1. Hidalgo-Curtis C et al 30697976 2019 A novel fusion gene involving PDGFRB and GCC2 in a chronic eosinophilic leukemia patient harboring t(2;5)(q37;q31). Iriyama N et al 28751768 2017 Cytogenetically cryptic ZMYM2-FLT3 and DIAPH1-PDGFRB gene fusions in myeloid neoplasms with eosinophilia. Jawhar M et al 24628626 2014 ATF7IP as a novel PDGFRB fusion partner in acute lymphoblastic leukaemia in children. Kobayashi K et al 10910073 2000 Fusion of H4/D10S170 to the platelet-derived growth factor receptor beta in BCR-ABL-negative myeloproliferative disorders with a t(5;10)(q33;q21). Kulkarni S et al 17301821 2007 A new NDE1/PDGFRB fusion transcript underlying chronic myelomonocytic leukaemia in Noonan Syndrome. La Starza R et al 15496975 2005 KIAA1509 is a novel PDGFRB fusion partner in imatinib-responsive myeloproliferative disease associated with a t(5;14)(q33;q32). Levine RL et al 22619110 2012 Identification of a novel partner gene, TPR, fused to FGFR1 in 8p11 myeloproliferative syndrome. Li F et al 11588050 2001 Rabaptin-5 is a novel fusion partner to platelet-derived growth factor beta receptor in chronic myelomonocytic leukemia. Magnusson MK et al 20164854 2010 KANK1, a candidate tumor suppressor gene, is fused to PDGFRB in an imatinib-responsive myeloid neoplasm with severe thrombocythemia. Medves S et al 15087372 2004 HCMOGT-1 is a novel fusion partner to PDGFRB in juvenile myelomonocytic leukemia with t(5;17)(q33;p11.2). Morerio C et al 25501022 2014 A novel fusion of SQSTM1 and FGFR1 in a patient with acute myelomonocytic leukemia with t(5;8)(q35;p11) translocation. Nakamura Y et al 26355392 2015 Fusion of PDGFRB to MPRIP, CPSF6, and GOLGB1 in three patients with eosinophilia-associated myeloproliferative neoplasms. Naumann N et al 9949182 1999 The t(6;8)(q27;p11) translocation in a stem cell myeloproliferative disorder fuses a novel gene, FOP, to fibroblast growth factor receptor 1. Popovici C et al 28408464 2017 Targetable kinase gene fusions in high-risk B-ALL: a study from the Children's Oncology Group. Reshmi SC et al 16838028 2006 TPM3/PDGFRB fusion transcript and its reciprocal in chronic eosinophilic leukemia. Rosati R et al 9616134 1998 Fusion of Huntingtin interacting protein 1 to platelet-derived growth factor beta receptor (PDGFbetaR) in chronic myelomonocytic leukemia with t(5;7)(q33;q11.2). Ross TS et al 15034867 2004 Molecular and cytogenetic characterization of a novel translocation t(4;22) involving the breakpoint cluster region and platelet-derived growth factor receptor-alpha genes in a patient with atypical chronic myeloid leukemia. Safley AM et al 16498388 2006 Identification of a novel imatinib responsive KIF5B-PDGFRA fusion gene following screening for PDGFRA overexpression in patients with hypereosinophilia. Score J et al 28261327 2017 Multiple MYO18A-PDGFRB fusion transcripts in a myeloproliferative neoplasm patient with t(5;17)(q32;q11). Sheng G et al 19369959 2009 LRRFIP1, a new FGFR1 partner gene associated with 8p11 myeloproliferative syndrome. Soler G et al 26319757 2015 A novel FOXP1-PDGFRA fusion gene in myeloproliferative neoplasm with eosinophilia. Sugimoto Y et al 29767670 2018 Treatment of the myeloid/lymphoid neoplasm with FGFR1 rearrangement with FGFR1 inhibitor. Verstovsek S et al 15087377 2004 NIN, a gene encoding a CEP110-like centrosomal protein, is fused to PDGFRB in a patient with a t(5;14)(q33;q24) and an imatinib-responsive myeloproliferative disorder. Vizmanos JL et al 15800673 2005 The t(8;17)(p11;q23) in the 8p11 myeloproliferative syndrome fuses MYO18A to FGFR1. Walz C et al 16845659 2006 Transient response to imatinib in a chronic eosinophilic leukemia associated with ins(9;4)(q33;q12q25) and a CDK5RAP2-PDGFRA fusion gene. Walz C et al 17296564 2007 Characterization of three new imatinib-responsive fusion genes in chronic myeloproliferative disorders generated by disruption of the platelet-derived growth factor receptor beta gene. Walz C et al 21330321 2011 The kinase inhibitor TKI258 is active against the novel CUX1-FGFR1 fusion detected in a patient with T-lymphoblastic leukemia/lymphoma and t(7;8)(q22;p11). Wasag B et al 23835704 2013 Tyrosine kinase inhibitor therapy induces remission in a patient with refractory EBF1-PDGFRB-positive acute lymphoblastic leukemia. Weston BW et al 9425908 1998 FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome. Xiao S et al 29284681 2018 A novel AGGF1-PDGFRb fusion in pediatric T-cell acute lymphoblastic leukemia. Zabriskie MS et al 29384404 2018 A novel fusion of PDGFRB to TSC1, an intrinsic suppressor of mTOR-signaling pathway, in a chronic eosinophilic leukemia patient with t(5;9)(q32;q34). Zhang Y et al 28449810 2017 Novel t(5;11)(q32;q13.4) with NUMA1-PDGFRB fusion in a myeloid neoplasm with eosinophilia with response to imatinib mesylate. Zou YS et al Citation Sheng  Xiao Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2: Overview 2019 Atlas Genet Cytogenet Oncol Haematol. 2019-07-01 Online version: http://atlasgeneticsoncology.org/haematological/1855/myeloid-lymphoid-neoplasms-with-eosinophilia-and-rearrangement-of-pdgfra-pdgfrb-or-fgfr1-or-with-pcm1-jak2-overview-2019 External Links OMIM database Cosmic database Genecards database Mitelman database Generate PDF × Please, confirm that you want to generate a PDF file of this page. This may take some seconds once process has started. Then it will be opened automatically. Wait a moment, we are generating the document... Generate PDF Aditional Info × Loading, wait... Close