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Created page with "{{Under Construction}} ==Primary Author(s)*== Yanna Ding, MD PhD __TOC__ ==Cancer Category/Type== Myeloid/lymphoid neoplasms ==Cancer Sub-Classification / Subtype== Mye..."

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{{Under Construction}}
==Primary Author(s)*==

Yanna Ding, MD PhD

__TOC__

==Cancer Category/Type==

Myeloid/lymphoid neoplasms

==Cancer Sub-Classification / Subtype==

Myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement

==Definition / Description of Disease==

Myeloid/lymphoid neoplasms with ''FGFR1'' rearrangement are a heterogenous group of aggressive neoplasms with translocations involving the fibroblast growth factor receptor 1(''FGFR1)'' tyrosine kinase gene on chromosome 8p11-12<ref name=":2">{{Cite journal|last=Jackson|first=Courtney C.|last2=Medeiros|first2=L. Jeffrey|last3=Miranda|first3=Roberto N.|date=2010|title=8p11 myeloproliferative syndrome: a review|url=http://www.sciencedirect.com/science/article/pii/S0046817709004067|journal=Human Pathology|volume=41|issue=4|pages=461–476|doi=10.1016/j.humpath.2009.11.003|issn=0046-8177}}</ref>. The neoplastic cells derive from a pluripotent haematopoietic stem cell and may be immature or mature<ref name=":0">Bain BJ, et al., (2017). Myeloid/lymphoid neoplasms with FGFR1 rearrangement in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p77-78.</ref>. Cases can present as a myeloproliferative neoplasm or as acute myeloid leukaemia, T- or B-lymphoblastic leukaemia/lymphoma or mixed-phenotype acute leukaemia. T-cell lymphoblastic lymphoma/leukemia is common, frequently with eosinophilia, and subsequently rapidly transforms into acute myeloid leukaemia.

Coexistence of atypical chronic myeloid leukaemia, ''BCR-ABL1''-negative, with t(8;19)(p11.2;q13.1) and ''KIT'' D816V-positive systemic mastocytosis with an associated haematological neoplasm has been reported <ref name=":6">{{Cite journal|last=Duckworth|first=Christina B|last2=Zhang|first2=Linsheng|last3=Li|first3=Shiyong|date=2014|title=Systemic mastocytosis with associated myeloproliferative neoplasm with t(8;19)(p12;q13.1) and abnormality of FGFR1: report of a unique case|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925931/|journal=International Journal of Clinical and Experimental Pathology|volume=7|issue=2|pages=801–807|issn=1936-2625|pmc=3925931|pmid=24551307}}</ref>.

==Synonyms / Terminology==

8p11 myeloproliferative syndrome (EMS)

8p11 stem cell syndrome

8p11 stem cell leukaemia/lymphoma syndrome

Haematopoietic stem cell neoplasm with FGFR1 abnormalities

Myeloid and lymphoid neoplasms with FGFR1 abnormalities <ref name=":0" />

==Epidemiology / Prevalence==

The median age at disease onset is 32 years, although it can occur within a wide age range of 3-84 years <ref name=":1">{{Cite journal|last=Macdonald|first=Donald|last2=Reiter|first2=Andreas|last3=Cross|first3=Nicholas C.P.|date=2002|title=The 8p11 Myeloproliferative Syndrome: A Distinct Clinical Entity Caused by Constitutive Activation of FGFR1|url=https://www.karger.com/Article/FullText/46639|journal=Acta Haematologica|language=en|volume=107|issue=2|pages=101–107|doi=10.1159/000046639|issn=0001-5792}}</ref>. There is a moderate predominance of male with male-to-female ratio of 1.5:1, unlike in myeloid/lymphoid neoplasms with ''[http://www.ccga.io/index.php/Myeloid/Lymphoid_Neoplasms_with_PDGFRA_Rearrangement#cite_ref-:0_1-4 PDGFRA]'' or ''PDGFRB'' rearrangement <ref name=":0" />.

==Clinical Features==

Systemic symptoms are common, including fatigue, fever, weight loss and night sweats. Some patients can be asymptomatic. Patients often present with peripheral blood eosinophilia without basophilia <ref name=":2" />. Cases with lymphoma features present as lymph nodes involvement and mediastinal mass; cases with myeloproliferative features present as splenomegaly and hypermetabolism. Cases can also present as acute myeloid leukaemia or myeloid sarcoma <ref name=":1" /> <ref>{{Cite journal|last=Abruzzo|first=Lynne V.|last2=Jaffe|first2=Elaine S.|last3=Cotelingam|first3=James D.|last4=Whang-Peng|first4=Jacqueline|last5=Duca|first5=Vincent Del|last6=Medeiros|first6=L. Jeffrey|date=1992|title=T-Cell Lymphoblastic Lymphoma With Eosinophilia Associated With Subsequent Myeloid Malignancy:|url=http://journals.lww.com/00000478-199203000-00003|journal=The American Journal of Surgical Pathology|language=en|volume=16|issue=3|pages=236–245|doi=10.1097/00000478-199203000-00003|issn=0147-5185}}</ref> <ref>{{Cite journal|last=Vega|first=Francisco|last2=Medeiros|first2=L. Jeffrey|last3=Bueso-Ramos|first3=Carlos E.|last4=Arboleda|first4=Patricia|last5=Miranda|first5=Roberto N.|date=2015|title=Hematolymphoid Neoplasms Associated With Rearrangements of PDGFRA, PDGFRB, and FGFR1|url=https://academic.oup.com/ajcp/article/144/3/377/1760716|journal=American Journal of Clinical Pathology|language=en|volume=144|issue=3|pages=377–392|doi=10.1309/AJCPMORR5Z2IKCEM|issn=1943-7722}}</ref>. Extranodal sites of disease include tonsil, lung, and breast in small subsets of patients <ref name=":2" />.

==Sites of Involvement==

Bone marrow, peripheral blood, lymph nodes, liver and spleen are primarily involved. Lymphoblasts or myeloid cells infiltration results in lymphadenopathy <ref name=":0" />.

==Morphologic Features==

Peripheral blood: Most cases have leukocytosis with increased neutrophils, bands, metamyelocytes, and myelocytes. Circulating blasts and eosinophilia are common. Monocytosis can be found. Hemoglobin levels have ranged from 6.3 to 21 g/dL and platelet counts have ranged from 8 to 546 × 10<sup>9</sup>/L<ref name=":2" />.

Bone marrow biopsy: often hypercellularity due to increased granulocytic precursors and eosinophilia. Hypocellular cases also exist. Many cases were interpreted as myeloid hyperplasia or myeloproliferative neoplasm, including chronic myelogenous leukemia, atypical chronic myeloid leukemia, or chronic myelomonocytic leukemia. Primary diagnoses also include myelodysplastic syndrome, myelodysplastic syndrome/myeloproliferative neoplasm due to dysplasia. 16% of the cases may have 20% or more blasts, in the range of acute leukemia with blasts of a myeloid lineage or bilineal lineage in two thirds of the cases, and of pure immature lymphoid lineage in one third of the cases <ref>{{Cite journal|last=Roy|first=Sukanya|last2=Szer|first2=Jeff|last3=Campbell|first3=Lynda J.|last4=Juneja|first4=Surender|date=2002|title=Sequential Transformation of t(8;13)-Related Disease|url=https://www.karger.com/Article/FullText/46637|journal=Acta Haematologica|language=en|volume=107|issue=2|pages=95–97|doi=10.1159/000046637|issn=0001-5792}}</ref>. Lymphoblastic lymphoma is more commonly seen in patients with t(8;13)<ref name=":6" />.

Lymph node biopsy: For patients who did undergo lymph node biopsy, 79% had T-lymphoblastic lymphoma and 21% myeloid sarcoma. Lymph nodes are infiltreated by small- or mediumsized lymphoblasts with fine or “dusty” chromatin and minimal cytoplasm. Eosinophils are frequently admixed with the lymphoblasts. Subtle myeloid component can be found in perivascular area. lymphoblastic component can be immunoreactive to TdT (terminal deoxynucleotidyl transferase), CD1a and pan-T-cell antigens while the subtle myeloid component can be positive for myeloperoxidase, CD15, CD68, CD117, lysozyme, or other myeloid-associated antigens<ref>{{Cite journal|last=Somers|first=Gino R.|last2=Slater|first2=Howard|last3=Rockman|first3=Steven|last4=Ekert|first4=Henry|last5=Southey|first5=Melissa C.|last6=Chow|first6=C.W.|last7=Armes|first7=Jane E.|last8=Venter|first8=Deon J.|date=1997|title=Coexistent T-Cell Lymphoblastic Lymphoma and an Atypical Myeloproliferative Disorder Associated with t(8;13)(p21;q14)|url=http://www.tandfonline.com/doi/full/10.1080/15513819709168354|journal=Pediatric Pathology & Laboratory Medicine|language=en|volume=17|issue=1|pages=141–158|doi=10.1080/15513819709168354|issn=1077-1042}}</ref> .

Basophilia can be found in cases with ''BCR-FGFR1'' fusion <ref>{{Cite journal|last=Roumiantsev|first=Sergei|last2=Krause|first2=Daniela S|last3=Neumann|first3=Carola A|last4=Dimitri|first4=Christopher A|last5=Asiedu|first5=Frances|last6=Cross|first6=Nicholas C.P|last7=Van Etten|first7=Richard A|date=2004|title=Distinct stem cell myeloproliferative/T lymphoma syndromes induced by ZNF198-FGFR1 and BCR-FGFR1 fusion genes from 8p11 translocations|url=https://linkinghub.elsevier.com/retrieve/pii/S1535610804000534|journal=Cancer Cell|language=en|volume=5|issue=3|pages=287–298|doi=10.1016/S1535-6108(04)00053-4}}</ref>, and in cases with t(1;8)(q31.1;p11.2)/''TRP-FGFR1'' fusion <ref>{{Cite journal|last=Li|first=Feng|last2=Zhai|first2=Yong-Ping|last3=Tang|first3=Yu-Mei|last4=Wang|first4=Li-Ping|last5=Wan|first5=Pin-Jun|date=2012|title=Identification of a novel partner gene, TPR, fused to FGFR1 in 8p11 myeloproliferative syndrome|url=http://doi.wiley.com/10.1002/gcc.21973|journal=Genes, Chromosomes and Cancer|language=en|volume=51|issue=9|pages=890–897|doi=10.1002/gcc.21973}}</ref>''.'' Polycythaemia vera has been reported in cases with t(6;8)(q27;p11.2)/''FGFR1OP-FGFR1'' fusion <ref>{{Cite journal|last=Vizmanos|first=José L|last2=Hernández|first2=Roberto|last3=Vidal|first3=María J|last4=Larráyoz|first4=María J|last5=Odero|first5=María D|last6=Marín|first6=Julián|last7=Ardanaz|first7=María T|last8=Calasanz|first8=María J|last9=Cross|first9=Nicholas C P|date=2004|title=Clinical variability of patients with the t(6;8)(q27;p12) and FGFR1OP-FGFR1 fusion: two further cases|url=http://www.nature.com/doifinder/10.1038/sj.thj.6200561|journal=The Hematology Journal|volume=5|issue=6|pages=534–537|doi=10.1038/sj.thj.6200561|issn=1466-4860}}</ref>.

==Immunophenotype==

Immunophenotypic analysis is not helpful in chronic phase disease. However, in lymphoblastic leukemia/lymphoma and in acute myeloid transformation, immunophenotypic analysis is important to distinguish the lineage origins, such as B- or T- lineage, or myeloid lineage <ref name=":0" />. Please refer to the above section "Morphologic Features".

==Chromosomal Rearrangements (Gene Fusions)==

Various translocations with an 8p11 breakpoint are found. Depending on the partners, a variety of fusion genes with part of ''FGFR1'' from 8p11 can be formed, encoding aberrant tyrosine kinases. Note: Some precise mapping has positioned ''FGFR1'' locus to 8p12, instead of 8p11 <ref>{{Cite journal|last=Mozziconacci|first=Marie-Joëlle|last2=Carbuccia|first2=Nadine|last3=Prebet|first3=Thomas|last4=Charbonnier|first4=Aude|last5=Murati|first5=Anne|last6=Vey|first6=Norbert|last7=Chaffanet|first7=Max|last8=Birnbaum|first8=Daniel|date=2008|title=Common features of myeloproliferative disorders with t(8;9)(p12;q33) and CEP110–FGFR1 fusion: Report of a new case and review of the literature|url=https://linkinghub.elsevier.com/retrieve/pii/S0145212607004444|journal=Leukemia Research|language=en|volume=32|issue=8|pages=1304–1308|doi=10.1016/j.leukres.2007.11.012}}</ref>.

{| class="wikitable sortable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Prevalence
|-
|t(8;13)(p11.2;q12.1)
|''ZMYM2-FGFR1''
|Most common, around 40% <ref>{{Cite journal|last=Popovici|first=C.|last2=Adelaide|first2=J.|last3=Ollendorff|first3=V.|last4=Chaffanet|first4=M.|last5=Guasch|first5=G.|last6=Jacrot|first6=M.|last7=Leroux|first7=D.|last8=Birnbaum|first8=D.|last9=Pebusque|first9=M.-J.|date=1998|title=Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13)(p12;q12)|url=http://www.pnas.org/cgi/doi/10.1073/pnas.95.10.5712|journal=Proceedings of the National Academy of Sciences|language=en|volume=95|issue=10|pages=5712–5717|doi=10.1073/pnas.95.10.5712|issn=0027-8424|pmc=PMC20444|pmid=9576949}}</ref><ref>{{Cite journal|last=Cross|first=Nicholas C. P.|last2=Goldman|first2=John M.|last3=Jennings|first3=Barbara A.|last4=Hernandez|first4=Jesus M.|last5=Gonçalves|first5=Cristina|last6=Aguiar|first6=Ricardo C. T.|last7=Macdonald|first7=Donald H. C.|last8=Chase|first8=Andrew|last9=Kulkarni|first9=Shashikant|date=1998|title=Consistent Fusion of ZNF198 to the Fibroblast Growth Factor Receptor-1 in the t(8;13)(p11;q12) Myeloproliferative Syndrome|url=https://ashpublications.org/blood/article/92/5/1735/247374/Consistent-Fusion-of-ZNF198-to-the-Fibroblast|journal=Blood|language=en|volume=92|issue=5|pages=1735–1742|doi=10.1182/blood.V92.5.1735|issn=0006-4971}}</ref><ref>{{Cite journal|last=Smedley|first=D|date=1998|title=The t(8;13)(p11;q11-12) rearrangement associated with an atypical myeloproliferative disorder fuses the fibroblast growth factor receptor 1 gene to a novel gene RAMP|url=https://academic.oup.com/hmg/article-lookup/doi/10.1093/hmg/7.4.637|journal=Human Molecular Genetics|volume=7|issue=4|pages=637–642|doi=10.1093/hmg/7.4.637}}</ref><ref name=":3">{{Cite journal|last=Xiao|first=Sheng|last2=Nalabolu|first2=Srinivasa R.|last3=Aster|first3=Jon C.|last4=Ma|first4=Junli|last5=Abruzzo|first5=Lynne|last6=Jaffe|first6=Elaine S.|last7=Stone|first7=Richard|last8=Weissman|first8=Sherman M.|last9=Hudson|first9=Thomas J.|date=1998|title=FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome|url=http://www.nature.com/articles/ng0198-84|journal=Nature Genetics|language=en|volume=18|issue=1|pages=84–87|doi=10.1038/ng0198-84|issn=1061-4036}}</ref><ref>{{Cite journal|last=Bain|first=Barbara J.|last2=Fletcher|first2=Sarah H.|date=2007-08|title=Chronic Eosinophilic Leukemias and the Myeloproliferative Variant of the Hypereosinophilic Syndrome|url=http://dx.doi.org/10.1016/j.iac.2007.06.001|journal=Immunology and Allergy Clinics of North America|volume=27|issue=3|pages=377–388|doi=10.1016/j.iac.2007.06.001|issn=0889-8561}}</ref><ref name=":2" />
|-
|t(8;9)(p11.2;q33.2)
|''CNTRL-FGFR1''
|Around 17% <ref name=":2" /><ref>{{Cite journal|last=Pébusque|first=Marie-Josèphe|last2=Rattner|first2=Jérome B.|last3=Birnbaum|first3=Daniel|last4=Dastugue|first4=Nicole|last5=Popovici|first5=Cornel|last6=Mack|first6=Gary J.|last7=Guasch|first7=Géraldine|date=2000|title=FGFR1 is fused to the centrosome-associated proteinCEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33)|url=https://ashpublications.org/blood/article/95/5/1788/138772/FGFR1-is-fused-to-the-centrosome-associated|journal=Blood|language=en|volume=95|issue=5|pages=1788–1796|doi=10.1182/blood.V95.5.1788.005k15_1788_1796|issn=0006-4971}}</ref>
|-
|t(6;8)(q27;p11.2)
|''FGFR1OP-FGFR1''
|Around 9% <ref name=":2" /> <ref>{{Cite journal|last=Pébusque|first=Marie-Josèphe|last2=Birnbaum|first2=Daniel|last3=Lafage-Pochitaloff|first3=Marina|last4=Jonveaux|first4=Philippe|last5=Grégoire|first5=Marie-José|last6=Zhang|first6=Bin|last7=Popovici|first7=Cornel|date=1999|title=The t(6;8)(q27;p11) Translocation in a Stem Cell Myeloproliferative Disorder Fuses a Novel Gene, FOP, to Fibroblast Growth Factor Receptor 1|url=https://ashpublications.org/blood/article/93/4/1381/258789/The-t-6-8-q27-p11-Translocation-in-a-Stem-Cell|journal=Blood|language=en|volume=93|issue=4|pages=1381–1389|doi=10.1182/blood.V93.4.1381|issn=0006-4971}}</ref>
|-
|t(8;22)(p11.2;q11.2)
|''BCR-FGFR1''
|At least eight cases<ref>{{Cite journal|last=Steer|first=E. J.|last2=Demiroglu|first2=A.|last3=Heath|first3=C.|last4=Pourgourides|first4=E.|last5=Taylor|first5=K.|last6=Bentley|first6=M.|last7=Allen|first7=S. L.|last8=Koduru|first8=P.|last9=Brody|first9=J. P.|date=2001|others=E. J. Steer, A. Demiroglu, C. Heath, E. Pourgourides, K. Taylor, M. Bentley|title=The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins|url=https://eprints.soton.ac.uk/60717/|journal=Blood|volume=98|pages=pp.468A|issn=0006-4971}}</ref><ref>{{Cite journal|last=Ågerstam|first=Helena|last2=Lilljebjörn|first2=Henrik|last3=Lassen|first3=Carin|last4=Swedin|first4=Agneta|last5=Richter|first5=Johan|last6=Vandenberghe|first6=Peter|last7=Johansson|first7=Bertil|last8=Fioretos|first8=Thoas|date=2007|title=Fusion gene-mediated truncation ofRUNX1 as a potential mechanism underlying disease progression in the 8p11 myeloproliferative syndrome|url=http://doi.wiley.com/10.1002/gcc.20442|journal=Genes, Chromosomes and Cancer|language=en|volume=46|issue=7|pages=635–643|doi=10.1002/gcc.20442}}</ref><ref>{{Cite journal|last=Liu|first=Jing|last2=Meng|first2=Li|date=2018|title=8p11 Myeloproliferative syndrome with t(8;22)(p11;q11): A case report|url=http://www.spandidos-publications.com/10.3892/etm.2018.6328|journal=Experimental and Therapeutic Medicine|doi=10.3892/etm.2018.6328|issn=1792-0981|pmc=PMC6090294|pmid=30116393}}</ref><ref>{{Cite journal|last=Fioretos|first=Thoas|last2=Panagopoulos|first2=Ioannis|last3=Lassen|first3=Carin|last4=Swedin|first4=Agneta|last5=Billström|first5=Rolf|last6=Isaksson|first6=Margareth|last7=Strömbeck|first7=Bodil|last8=Olofsson|first8=Tor|last9=Mitelman|first9=Felix|date=2001|title=Fusion of the BCR and the fibroblast growth factor receptor-1 ( FGFR1 ) genes as a result of t(8;22)(p11;q11) in a myeloproliferative disorder: The first fusion gene involving BCR but not ABL: Fusion of the BCR and FGFR1 Genes|url=http://doi.wiley.com/10.1002/gcc.1195|journal=Genes, Chromosomes and Cancer|language=en|volume=32|issue=4|pages=302–310|doi=10.1002/gcc.1195}}</ref><ref>{{Cite journal|last=Pini|first=Massimo|last2=Gottardi|first2=Enrico|last3=Scaravaglio|first3=Patrizia|last4=Giugliano|first4=Emilia|last5=Libener|first5=Roberta|last6=Baraldi|first6=Anna|last7=Muzio|first7=Alberto|last8=Cornaglia|first8=Elisa|last9=Saglio|first9=Giuseppe|date=2002|title=A fourth case of BCR-FGFR1 positive CML-like disease with t(8;22) translocation showing an extensive deletion on the derivative chromosome 8p|url=http://www.nature.com/doifinder/10.1038/sj.thj.6200201|journal=The Hematology Journal|volume=3|issue=6|pages=315–316|doi=10.1038/sj.thj.6200201}}</ref>
|-
|t(7;8)(q33;p11.2)
|''TRIM24-FGFR1''
|At least two cases <ref>{{Cite journal|last=Belloni|first=Elena|last2=Trubia|first2=Maurizio|last3=Gasparini|first3=Patrizia|last4=Micucci|first4=Carla|last5=Tapinassi|first5=Cinzia|last6=Confalonieri|first6=Stefano|last7=Nuciforo|first7=Paolo|last8=Martino|first8=Bruno|last9=Lo‐Coco|first9=Francesco|date=2005|title=8p11 myeloproliferative syndrome with a novel t(7;8) translocation leading to fusion of the FGFR1 and TIF1 genes|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/gcc.20144|journal=Genes, Chromosomes and Cancer|language=en|volume=42|issue=3|pages=320–325|doi=10.1002/gcc.20144|issn=1098-2264}}</ref><ref name=":4">{{Cite journal|last=Sohal|first=Jastinder|last2=Chase|first2=Andrew|last3=Mould|first3=Sarah|last4=Corcoran|first4=Martin|last5=Oscier|first5=David|last6=Iqbal|first6=Sameena|last7=Parker|first7=Sally|last8=Welborn|first8=Jeanna|last9=Harris|first9=Richard I.|date=2001|title=Identification of four new translocations involvingFGFR1 in myeloid disorders|url=http://doi.wiley.com/10.1002/gcc.1177|journal=Genes, Chromosomes and Cancer|language=en|volume=32|issue=2|pages=155–163|doi=10.1002/gcc.1177|issn=1045-2257}}</ref>
|-
|t(8;17)(p11.2;q23)
|''MYO18A-FGFR1''
|At least one case<ref>{{Cite journal|last=Walz|first=C|last2=Chase|first2=A|last3=Schoch|first3=C|last4=Weisser|first4=A|last5=Schlegel|first5=F|last6=Hochhaus|first6=A|last7=Fuchs|first7=R|last8=Schmitt-Gräff|first8=A|last9=Hehlmann|first9=R|date=2005|title=The t(8;17)(p11;q23) in the 8p11 myeloproliferative syndrome fuses MYO18A to FGFR1|url=http://www.nature.com/articles/2403712|journal=Leukemia|language=en|volume=19|issue=6|pages=1005–1009|doi=10.1038/sj.leu.2403712|issn=0887-6924}}</ref>
|-
|t(8;19)(p11.2;q13.3)
|''HERVK-FGFR1''
|At least one case <ref>{{Cite journal|last=Mugneret|first=Francine|last2=Chaffanet|first2=Max|last3=Maynadie|first3=Marc|last4=Guasch|first4=Geraldine|last5=Favre|first5=Bernardine|last6=Casasnovas|first6=Olivier|last7=Birnbaum|first7=Daniel|last8=Pebusque|first8=Marie-Josephe|date=2000|title=The 8p12 myeloproliferative disorder. t(8;19)(p12;q13.3): a novel translocation involving the FGFR1 gene . SHORT REPORT|url=http://doi.wiley.com/10.1046/j.1365-2141.2000.02355.x|journal=British Journal of Haematology|language=en|volume=111|issue=2|pages=647–649|doi=10.1046/j.1365-2141.2000.02355.x|issn=0007-1048}}</ref><ref name=":5">{{Cite journal|last=Pébusque|first=Marie-Josèphe|last2=Birnbaum|first2=Daniel|last3=Pontarotti|first3=Pierre|last4=Chaffanet|first4=Max|last5=Mugneret|first5=Francine|last6=Popovici|first6=Cornel|last7=Guasch|first7=Géraldine|date=2003|title=Endogenous retroviral sequence is fused to FGFR1 kinase in the 8p12 stem-cell myeloproliferative disorder with t(8;19)(p12;q13.3)|url=https://ashpublications.org/blood/article/101/1/286/89004/Endogenous-retroviral-sequence-is-fused-to-FGFR1|journal=Blood|language=en|volume=101|issue=1|pages=286–288|doi=10.1182/blood-2002-02-0577|issn=0006-4971}}</ref>
|-
|ins(12;8)(p11.2;p11.2p22)
|''FGFR1OP2-FGFR1''
|At least two cases <ref name=":4" /><ref>{{Cite journal|last=Grand|first=Effie K.|last2=Grand|first2=Francis H.|last3=Chase|first3=Andrew J.|last4=Ross|first4=Fiona M.|last5=Corcoran|first5=Martin M|last6=Oscier|first6=David G.|last7=Cross|first7=Nicholas C. P.|date=2004|title=Identification of a novel gene,FGFR1OP2, fused toFGFR1 in 8p11 myeloproliferative syndrome|url=http://doi.wiley.com/10.1002/gcc.20023|journal=Genes, Chromosomes and Cancer|language=en|volume=40|issue=1|pages=78–83|doi=10.1002/gcc.20023|issn=1045-2257}}</ref>
|-
|t(1;8)(q31.1;p11.2)
|''TRP-FGFR1''
|At least one case <ref>{{Cite journal|last=Li|first=Feng|last2=Zhai|first2=Yong-Ping|last3=Tang|first3=Yu-Mei|last4=Wang|first4=Li-Ping|last5=Wan|first5=Pin-Jun|date=2012|title=Identification of a novel partner gene, TPR, fused to FGFR1 in 8p11 myeloproliferative syndrome|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/gcc.21973|journal=Genes, Chromosomes and Cancer|language=en|volume=51|issue=9|pages=890–897|doi=10.1002/gcc.21973|issn=1098-2264}}</ref>
|-
|t(2;8)(q13;p11.2)
|''RANBP2-FGFR1''
|At least one case <ref>{{Cite journal|last=Mauvieux|first=L.|last2=Bilger|first2=K.|last3=Herbrecht|first3=R.|last4=Ittel|first4=A.|last5=A.-C. Galoisy|last6=Jeandidier|first6=E.|last7=Hélias|first7=C.|last8=Perrusson|first8=N.|last9=Dano|first9=L.|date=2013|title=A translocation t(2;8)(q12;p11) fuses FGFR1 to a novel partner gene, RANBP2/NUP358 , in a myeloproliferative/myelodysplastic neoplasm|url=https://www.nature.com/articles/leu2012286|journal=Leukemia|language=en|volume=27|issue=5|pages=1186–1188|doi=10.1038/leu.2012.286|issn=1476-5551}}</ref>
|-
|t(2;8)(q37.3;p11.2)
|''LRRFIP1-FGFR1''
|At least one case <ref>{{Cite journal|last=Soler|first=G|last2=Nusbaum|first2=S|last3=Varet|first3=B|last4=Macintyre|first4=E A|last5=Vekemans|first5=M|last6=Romana|first6=S P|last7=Radford-Weiss|first7=I|date=2009|title=LRRFIP1, a new FGFR1 partner gene associated with 8p11 myeloproliferative syndrome|url=http://www.nature.com/articles/leu200979|journal=Leukemia|language=en|volume=23|issue=7|pages=1359–1361|doi=10.1038/leu.2009.79|issn=0887-6924}}</ref>
|-
|t(7;8)(q22.1;p11.2)
|''CUX1-FGFR1''
|At least one case <ref>{{Cite journal|last=Wasag|first=B.|last2=Lierman|first2=E.|last3=Meeus|first3=P.|last4=Cools|first4=J.|last5=Vandenberghe|first5=P.|date=2011|title=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)|url=http://www.haematologica.org/cgi/doi/10.3324/haematol.2010.036558|journal=Haematologica|language=en|volume=96|issue=6|pages=922–926|doi=10.3324/haematol.2010.036558|issn=0390-6078|pmc=PMC3105656|pmid=21330321}}</ref>
|-
|t(8;12)(p11.2;q15)
|''CPSF6-FGFR1''
|At least two cases <ref name=":4" /><ref>{{Cite journal|last=Bae|first=Sook Young|last2=Kim|first2=Jang Su|last3=Han|first3=Eun Ae|last4=Lee|first4=Hae Jin|last5=Ryeu|first5=Bung Jun|last6=Lee|first6=Kap No|last7=Lee|first7=Chang Kyu|last8=Cho|first8=Yunjung|last9=Kim|first9=Young Kee|date=2009|title=Cytogenetic abnormality involving 8p11.2 in T-lymphoblastic lymphoma: report of a new case|url=https://linkinghub.elsevier.com/retrieve/pii/S0165460809000867|journal=Cancer Genetics and Cytogenetics|language=en|volume=191|issue=1|pages=57–58|doi=10.1016/j.cancergencyto.2009.02.003}}</ref>
|-
|t(5;8)(q35;p11)
|SQSTM1-FGFR1
|One case <ref>{{Cite journal|last=Bessho|first=M.|last2=Uchida|first2=Y.|last3=E. Kakegawa|last4=Wakimoto|first4=N.|last5=Ito|first5=Y.|last6=Nakamura|first6=Y.|date=2014|title=A novel fusion of SQSTM1 and FGFR1 in a patient with acute myelomonocytic leukemia with t(5;8)(q35;p11) translocation|url=https://www.nature.com/articles/bcj201486|journal=Blood Cancer Journal|language=en|volume=4|issue=12|pages=e265–e265|doi=10.1038/bcj.2014.86|issn=2044-5385|pmc=PMC4315892|pmid=25501022}}</ref>
|}

==Characteristic Chromosomal Aberrations / Patterns==

A variety of translocations involving 8p11 breakpoint. Secondary cytogenetic abnormalities also occur, most commonly trisomy 21 <ref name=":0" />.

==Genes and Main Pathways Involved==

Normal FGFR1 is a transmembrane protein with an extracellular ligand-binding domain, a transmembrane domain and a cytoplasmic tyrosine kinase domain. In inactive state, FGFR1 presents as monomers in cell membrane. Binding with ligands--the fibroblast growth factors (FGFs), induces dimerization and a conformational change that partially activates the enzymatic activity leading to transphosphorylation of the key tyrosine residue, an increase in enzymatic activity, phosphorylation of additional tyrosines and subsequent phosphorylation of downstream target substrates. The signaling pathways include Ras/MAPK, P13K, PLCÁ and STAT proteins. Fusion proteins with FGFR1 mimic the initial tyrosine kinase activation and thus possess constitutive tyrosine kinase activity to activate multiple signal transduction pathways in myeloid/lymphoid neoplasms <ref>{{Cite journal|last=Ollendorff|first=Vincent|last2=Guasch|first2=Géraldine|last3=Isnardon|first3=Daniel|last4=Galindo|first4=Rémy|last5=Birnbaum|first5=Daniel|last6=Pébusque|first6=Marie-Josèphe|date=1999|title=Characterization of FIM-FGFR1, the Fusion Product of the Myeloproliferative Disorder-associated t(8;13) Translocation|url=http://www.jbc.org/lookup/doi/10.1074/jbc.274.38.26922|journal=Journal of Biological Chemistry|language=en|volume=274|issue=38|pages=26922–26930|doi=10.1074/jbc.274.38.26922|issn=0021-9258}}</ref><ref>{{Cite journal|last=Jiang|first=Guoqiang|last2=den Hertog|first2=Jeroen|last3=Hunter|first3=Tony|date=2000|title=Receptor-Like Protein Tyrosine Phosphatase α Homodimerizes on the Cell Surface|url=https://mcb.asm.org/content/20/16/5917|journal=Molecular and Cellular Biology|language=en|volume=20|issue=16|pages=5917–5929|doi=10.1128/MCB.20.16.5917-5929.2000|issn=1098-5549|pmc=PMC86069|pmid=10913175}}</ref><ref>{{Cite journal|last=Mason|first=Ivor J.|date=1994|title=The ins and outs of fibroblast growth factors|url=https://linkinghub.elsevier.com/retrieve/pii/0092867494905207|journal=Cell|language=en|volume=78|issue=4|pages=547–552|doi=10.1016/0092-8674(94)90520-7}}</ref><ref>{{Cite journal|last=Smedley|first=Damian|last2=Demiroglu|first2=Asuman|last3=Abdul-Rauf|first3=Munah|last4=Heatht|first4=Carol|last5=Cooper|first5=Colin|last6=Shipley|first6=Janet|last7=Cross|first7=Nicholas C.P.|date=1999|title=ZNF198-FGFR1 Transforms Ba/F3 Cells to Growth Factor Independence and Results in High Level Tyrosine Phosphorylation of STATS 1 and 5|url=https://linkinghub.elsevier.com/retrieve/pii/S1476558699800268|journal=Neoplasia|language=en|volume=1|issue=4|pages=349–355|doi=10.1038/sj.neo.7900035|pmc=PMC1508104|pmid=10935490}}</ref>.

==Diagnostic Testing Methods==

Diagnosis is based on integration of morphology, immunophenotype, cytogenetics analysis and molecular analysis. Identification of translocations involving ''FGFR1'' and the corresponding fusion genes is diagnostic in the setting of myeloid or lymphoid neoplasm with prominent eosinophilia. Conventional cytogenetic analysis is useful since almost all the translocations or insertions involving ''FGFR1'' have been cytogenetically visible <ref>A. Meloni-Ehrig (2013), The Cytogenetics of Hematologic Neoplasms in The Principles of Clinical Cytogenetics. 4<sup>th</sup> edition, '''Gersen''', Steven L., '''Keagle''', Martha B. <nowiki>ISBN 978-1-4899-9720-3</nowiki>, p320</ref><ref name=":2" />. Translocations of ''FGFR1'' and the associated fusion genes can be more specifically detected by two-color fluorescence in situ hybridization (FISH), and reverse transcriptase–polymerase chain reaction (RT-PCR) <ref name=":3" /> <ref name=":5" /><ref>{{Cite journal|last=Cowell|first=John K.|last2=Stone|first2=Richard M.|last3=Hurd|first3=David|last4=Chernova|first4=Olga|last5=Still|first5=Ivan H.|date=1997|title=Molecular Characterization of the t(8; 13)(p11;q12) Translocation Associated With an Atypical Myeloproliferative Disorder: Evidence for Three Discrete Loci Involved in Myeloid Leukemias on 8p11|url=https://ashpublications.org/blood/article/90/8/3136/139329/Molecular-Characterization-of-the-t-8-13-p11-q12|journal=Blood|language=en|volume=90|issue=8|pages=3136–3141|doi=10.1182/blood.V90.8.3136|issn=0006-4971}}</ref>.

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==

Unlike myeloid/lymphoid neoplasms with ''[[Myeloid/Lymphoid Neoplasms with PDGFRA Rearrangement#cite ref-:0 1-4|PDGFRA]]'' or ''PDGFRB'' rearrangement, the prognosis for this ''FGFR1'' associated entity is poor even for patient in the chronic phase, due to the high incidence of transformation. There is no established tyrosine kinase inhibitor therapy for myeloproliferative neoplasms with ''FGFR1'' rearrangement. Midostaurin (PKC412) was reported to be effective in one case <ref>{{Cite journal|last=Chen|first=J.|last2=DeAngelo|first2=D. J.|last3=Kutok|first3=J. L.|last4=Williams|first4=I. R.|last5=Lee|first5=B. H.|last6=Wadleigh|first6=M.|last7=Duclos|first7=N.|last8=Cohen|first8=S.|last9=Adelsperger|first9=J.|date=2004|title=PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder|url=http://www.pnas.org/cgi/doi/10.1073/pnas.0404438101|journal=Proceedings of the National Academy of Sciences|language=en|volume=101|issue=40|pages=14479–14484|doi=10.1073/pnas.0404438101|issn=0027-8424|pmc=PMC521956|pmid=15448205}}</ref>, and interferon has induced cytogenetic response in several cases <ref name=":1" /> <ref>{{Cite journal|last=Holmes|first=A L|last2=Raper|first2=R N|last3=Heilig|first3=J S|date=1998|title=Genetic analysis of Drosophila larval optic nerve development.|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1460051/|journal=Genetics|volume=148|issue=3|pages=1189–1201|issn=0016-6731|pmc=1460051|pmid=9539434}}</ref>. Nevertheless, haematopoietic stem cell transplantation should be considered even for patients in chronic phase.

==Familial Forms==

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==Other Information==

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==Links==

[[FGFR1]]

==References==

===EXAMPLE Book===

#Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p129-171.

==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.
<references />

HAEM4:Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement - Revision history

Bailey.Glen at 18:41, 3 November 2023

Bailey.Glen: Created page with "{{Under Construction}} ==Primary Author(s)*== Yanna Ding, MD PhD TOC ==Cancer Category/Type== Myeloid/lymphoid neoplasms ==Cancer Sub-Classification / Subtype== Mye..."

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 {{Under Construction}}
 ==Primary Author(s)*==
@@ Line 160: / Line 165: @@
 <nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
 <references />

HAEM4:Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement - Revision history

Bailey.Glen at 18:41, 3 November 2023

Bailey.Glen: Created page with "{{Under Construction}} ==Primary Author(s)*== Yanna Ding, MD PhD __TOC__ ==Cancer Category/Type== Myeloid/lymphoid neoplasms ==Cancer Sub-Classification / Subtype== Mye..."

Bailey.Glen: Created page with "{{Under Construction}} ==Primary Author(s)*== Yanna Ding, MD PhD TOC ==Cancer Category/Type== Myeloid/lymphoid neoplasms ==Cancer Sub-Classification / Subtype== Mye..."