A Neoplasm with FIP1L1-PDGFRA Fusion Presenting As Pediatric T-cell Lymphoblastic Leukemia/lymphoma Without Eosinophilia

Overview

Journal Cancer Genet

Publisher Elsevier

Specialty Oncology

Date 2017 Oct 14

PMID 29025601

Citations 4

Authors

Matthew J Oberley

Christopher Denton

Jianling Ji

Matthew Hiemenz

Deepa Bhojwani

Dejerianne Ostrow

Samuel Wu

Paul Gaynon

Gordana Raca

Affiliations

Soon will be listed here.

Abstract

The 2016 World Health Organization (2016 WHO) classification of hematopoietic malignancies classifies neoplasms with a fusion between the FIP1L1 and PDGFRA genes in 4q12 into a group called "myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1 or with PCM1-JAK2". Neoplasms characterized by this fusion are pluripotent stem cell disorders that can show both myeloid and lymphoid differentiation. They typically occur in adult patients and most are characterized by eosinophilia. We describe identification of a FIP1L1-PDGFRA fusion in a 13-year-old boy who presented with T-lymphoblastic leukemia/lymphoma without eosinophilia. Detection of FIP1L1-PDGFRA driven neoplasms at diagnosis is usually critical for proper treatment, since almost all reported cases responded to tyrosine kinase inhibitors. However, our patient's leukemia was refractory to standard chemotherapy, and did not show a meaningful response to tyrosine kinase inhibitor therapy. Testing for a FIP1L1-PDGFRA rearrangement is at present limited to patients with idiopathic hypereosinophilia, and we hypothesize that this abnormality may be under-diagnosed in children with acute leukemias.

Citing Articles

FIP1L1::PDGFRA Fusion in a Pediatric Patient Presenting With B-Cell Lymphoblastic Leukemia.

Nunn J, Williams B, Deambrosis D Genes Chromosomes Cancer. 2025; 64(2):e70037.

PMID: 39996417 PMC: 11851426. DOI: 10.1002/gcc.70037.

Integration of Genomic Sequencing Drives Therapeutic Targeting of PDGFRA in T-Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma.

Paolino J, Dimitrov B, Winger B, Sandoval-Perez A, Rangarajan A, Ocasio-Martinez N Clin Cancer Res. 2023; 29(22):4613-4626.

PMID: 37725576 PMC: 10872648. DOI: 10.1158/1078-0432.CCR-22-2562.

Case Report: Pediatric myeloid/lymphoid neoplasm with eosinophilia and PDGFRA rearrangement: The first case presenting as B-lymphoblastic lymphoma.

Akiely R, Almasri F, Almasri N, Abu-Ghosh A Front Pediatr. 2023; 10:1059527.

PMID: 36589160 PMC: 9794852. DOI: 10.3389/fped.2022.1059527.

Sustained Complete Molecular Remission With Imatinib Monotherapy in a Child Presenting With Blast Phase -Associated Myeloid Neoplasm With Eosinophilia.

Jain J, Weinzierl E, Saxe D, Bergsagel J, Gotlib J, Reiter A Hemasphere. 2020; 4(6):e486.

PMID: 33196011 PMC: 7655083. DOI: 10.1097/HS9.0000000000000486.

Complete response of myeloid/lymphoid neoplasms with PDGFRA rearrangement presenting as leukemia/myeloid sarcoma to imatinib monotherapy.

Ma R, Huang X, Jia J, Kong J, Qin Y, Jiang H Chin Med J (Engl). 2019; 132(20):2498-2500.

PMID: 31567386 PMC: 6831079. DOI: 10.1097/CM9.0000000000000437.

References

Cools J, DeAngelo D, Gotlib J, Stover E, Legare R, Cortes J . 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(13):1201-14. DOI: 10.1056/NEJMoa025217. View

Farruggia P, Giugliano E, Russo D, Trizzino A, Lorenzatti R, Santoro A . FIP1L1-PDGFRα-positive hypereosinophilic syndrome in childhood: a case report and review of literature. J Pediatr Hematol Oncol. 2013; 36(1):e28-30. DOI: 10.1097/MPH.0b013e31827e6386. View

Metzgeroth G, Walz C, Score J, Siebert R, Schnittger S, Haferlach C . Recurrent finding of the FIP1L1-PDGFRA fusion gene in eosinophilia-associated acute myeloid leukemia and lymphoblastic T-cell lymphoma. Leukemia. 2007; 21(6):1183-8. DOI: 10.1038/sj.leu.2404662. View

Legrand F, Renneville A, Macintyre E, Mastrilli S, Ackermann F, Cayuela J . The Spectrum of FIP1L1-PDGFRA-Associated Chronic Eosinophilic Leukemia: New Insights Based on a Survey of 44 Cases. Medicine (Baltimore). 2013; 92(5):e1-e9. PMC: 4553979. DOI: 10.1097/MD.0b013e3182a71eba. View

Rathe M, Kristensen T, Moller M, Carlsen N . Myeloid neoplasm with prominent eosinophilia and PDGFRA rearrangement treated with imatinib mesylate. Pediatr Blood Cancer. 2010; 55(4):730-2. DOI: 10.1002/pbc.22655. View

Vega F, Medeiros L, Bueso-Ramos C, Arboleda P, Miranda R . Hematolymphoid neoplasms associated with rearrangements of PDGFRA, PDGFRB, and FGFR1. Am J Clin Pathol. 2015; 144(3):377-92. DOI: 10.1309/AJCPMORR5Z2IKCEM. View

Heinrich M, Corless C, Duensing A, McGreevey L, Chen C, Joseph N . PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003; 299(5607):708-10. DOI: 10.1126/science.1079666. View

. Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014; 25 Suppl 3:iii21-6. DOI: 10.1093/annonc/mdu255. View

Arber D, Orazi A, Hasserjian R, Thiele J, Borowitz M, Le Beau M . The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016; 127(20):2391-405. DOI: 10.1182/blood-2016-03-643544. View

10.

Walz C, Score J, Mix J, Cilloni D, Roche-Lestienne C, Yeh R . The molecular anatomy of the FIP1L1-PDGFRA fusion gene. Leukemia. 2008; 23(2):271-8. DOI: 10.1038/leu.2008.310. View

11.

DAngio M, Valsecchi M, Testi A, Conter V, Nunes V, Parasole R . Clinical features and outcome of SIL/TAL1-positive T-cell acute lymphoblastic leukemia in children and adolescents: a 10-year experience of the AIEOP group. Haematologica. 2014; 100(1):e10-3. PMC: 4281327. DOI: 10.3324/haematol.2014.112151. View

12.

Metzgeroth G, Erben P, Martin H, Mousset S, Teichmann M, Walz C . Limited clinical activity of nilotinib and sorafenib in FIP1L1-PDGFRA positive chronic eosinophilic leukemia with imatinib-resistant T674I mutation. Leukemia. 2011; 26(1):162-4. DOI: 10.1038/leu.2011.181. View

13.

Lierman E, Michaux L, Beullens E, Pierre P, Marynen P, Cools J . FIP1L1-PDGFRalpha D842V, a novel panresistant mutant, emerging after treatment of FIP1L1-PDGFRalpha T674I eosinophilic leukemia with single agent sorafenib. Leukemia. 2009; 23(5):845-51. DOI: 10.1038/leu.2009.2. View

14.

Gotlib J, Cools J . Five years since the discovery of FIP1L1-PDGFRA: what we have learned about the fusion and other molecularly defined eosinophilias. Leukemia. 2008; 22(11):1999-2010. DOI: 10.1038/leu.2008.287. View

15.

Oliveira J, Kumar R, Khan S, Law M, Erickson-Johnson M, Oliveira A . Successful treatment of a child with T/myeloid acute bilineal leukemia associated with TLX3/BCL11B fusion and 9q deletion. Pediatr Blood Cancer. 2011; 56(3):467-9. DOI: 10.1002/pbc.22850. View

16.

Bain B . Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1. Haematologica. 2010; 95(5):696-8. PMC: 2864371. DOI: 10.3324/haematol.2009.021675. View

17.

Pardanani A, Lasho T, Barraco D, Patnaik M, Elala Y, Tefferi A . Next generation sequencing of myeloid neoplasms with eosinophilia harboring the FIP1L1-PDGFRA mutation. Am J Hematol. 2015; 91(3):E10-1. DOI: 10.1002/ajh.24273. View

18.

Girardi T, Vicente C, Cools J, De Keersmaecker K . The genetics and molecular biology of T-ALL. Blood. 2017; 129(9):1113-1123. PMC: 5363819. DOI: 10.1182/blood-2016-10-706465. View

19.

Rives S, Alcorta I, Toll T, Tuset E, Estella J, Cross N . Idiopathic hypereosinophilic syndrome in children: report of a 7-year-old boy with FIP1L1-PDGFRA rearrangement. J Pediatr Hematol Oncol. 2005; 27(12):663-5. DOI: 10.1097/01.mph.0000193467.06938.77. View

20.

Sulong S, Moorman A, Irving J, Strefford J, Konn Z, Case M . A comprehensive analysis of the CDKN2A gene in childhood acute lymphoblastic leukemia reveals genomic deletion, copy number neutral loss of heterozygosity, and association with specific cytogenetic subgroups. Blood. 2008; 113(1):100-7. DOI: 10.1182/blood-2008-07-166801. View