t(8;22)(p11;q11) BCR/FGFR1
2002-01-01 Nicholas C P Cross Affiliation1.Department of Molecular and Developmental Biology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan
Clinics and Pathology
Disease
Described in only 3 cases, all of whom had a CML-like (chronic myelogenous leukemia-like) disease. Two had also had an excesss of B-lymphocytes in the marrow.
Phenotype stem cell origin
Involvement of both myeloid and lymphoid cells, so likely to be a stem cell. disorder
Evolution
At the time of writing, one patient had undergone myeloid transformation and a second patient underwent lymphoid transformation followed shortly by myeloid transformation. In common with other patients with FGFR1 fusion genes, the disease therefore appears to be aggressive.
Genes Involved and Proteins
Gene name
FGFR1 (Fibroblast Growth Factor Receptor 1)
Location
8p11.23
Protein description
Receptor tyrosine kinase for FGF ligands, also involved in the t(6;8)(q27;p12), t(8;9)(p12;q32-34) and t(8;13)(p12;q12)
Gene name
BCR (Breakpoint cluster region)
Location
22q11.23
Protein description
Normal function unclear; fuses to ABL in CML .
Result of the Chromosomal Anomaly
Description
5BCR - 3FGFR1
Transcript
All three patients has BCR exon 4 fused to FGFR1 exon 9
Detection protocole
RT-PCR or FISH
Description
Contains the coiled-coil domain of BCR, the BCR Y177 Grb2 binding site and the entire tyrosine kinase domain of FGFR1.
Oncogenesis
Analogous to BCR-ABL: constitutive activation of FGFR1 tyrosine kinase. Transforms Ba/F3 cells to IL-3 independence. Transformed cells are not affected by imatinib (Gleevec/Glivec/STI571) but are inhibited by compounds with anti-FGFR activity.
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 27245147 | 2016 | FGFR inhibitors: Effects on cancer cells, tumor microenvironment and whole-body homeostasis (Review). | 137 |
| 17431132 | 2007 | Enhanced phosphorylation of Nbs1, a member of DNA repair/checkpoint complex Mre11-RAD50-Nbs1, can be targeted to increase the efficacy of imatinib mesylate against BCR/ABL-positive leukemia cells. | 74 |
| 35574218 | 2022 | Proteomic analysis reveals dual requirement for Grb2 and PLCγ1 interactions for BCR-FGFR1-Driven 8p11 cell proliferation. | 54 |
| 29367757 | 2018 | The miR-17/92 cluster is involved in the molecular etiology of the SCLL syndrome driven by the BCR-FGFR1 chimeric kinase. | 50 |
| 31980503 | 2020 | Functional characterization of two rare BCR-FGFR1(+) leukemias. | 39 |
| 31439673 | 2020 | Oncogenic fusion protein BCR-FGFR1 requires the breakpoint cluster region-mediated oligomerization and chaperonin Hsp90 for activation. | 37 |
| 30413411 | 2019 | Loss of the BCR-FGFR1 GEF Domain Suppresses RHOA Activation and Enhances B-Lymphomagenesis in Mice. | 32 |
| 23082258 | 2012 | Allogeneic Hematopoietic Stem Cell Transplantation for a BCR-FGFR1 Myeloproliferative Neoplasm Presenting as Acute Lymphoblastic Leukemia. | 30 |
| 29735550 | 2018 | miR-339 Promotes Development of Stem Cell Leukemia/Lymphoma Syndrome via Downregulation of the BCL2L11 and BAX Proapoptotic Genes. | 28 |
| 22701616 | 2012 | Acute progression of BCR-FGFR1 induced murine B-lympho/myeloproliferative disorder suggests involvement of lineages at the pro-B cell stage. | 21 |
| 30647980 | 2018 | A Case of Myeloproliferative Neoplasm with BCR-FGFR1 Rearrangement: Favorable Outcome after Haploidentical Allogeneic Transplantation. | 21 |
| 22875613 | 2013 | Ponatinib as targeted therapy for FGFR1 fusions associated with the 8p11 myeloproliferative syndrome. | 19 |
| 23519513 | 2013 | A case of acute myelogenous leukaemia characterised by the BCR-FGFR1 translocation. | 18 |
| 27313753 | 2016 | Chronic myelogenous leukemia-like hematological malignancy with t(8;22) in a 26-year-old pregnant woman: A case report. | 18 |
| 30116393 | 2018 | 8p11 Myeloproliferative syndrome with t(8;22)(p11;q11): A case report. | 16 |
| 36698221 | 2023 | Myeloid/lymphoid neoplasm with eosinophilia and BCR/FGFR1 rearrangement with transformation to cortical T-lymphoblastic lymphoma and erythroid precursors: a case report. | 11 |
| 27785808 | 2016 | A model of BCR-FGFR1 driven human AML in immunocompromised mice. | 10 |
| 31525277 | 2020 | Critical individual roles of the BCR and FGFR1 kinase domains in BCR-FGFR1-driven stem cell leukemia/lymphoma syndrome. | 0 |
| 28551329 | 2017 | Myeloproliferative neoplasms with t(8;22)(p11.2;q11.2)/BCR-FGFR1: a meta-analysis of 20 cases shows cytogenetic progression with B-lymphoid blast phase. | 0 |
| 15870860 | 2005 | Dual lympho-myeloproliferative disorder in a patient with t(8;22) with BCR-FGFR1 gene fusion. | 0 |
| 15050920 | 2004 | Distinct stem cell myeloproliferative/T lymphoma syndromes induced by ZNF198-FGFR1 and BCR-FGFR1 fusion genes from 8p11 translocations. | 0 |
| 34551378 | 2021 | A rare case of atypical chronic myeloid leukemia associated with t(8;22)(p11.2;q11.2)/ BCR-FGFR1 rearrangement: A case report and literature review. | 0 |
| 36965231 | 2023 | Synergetic effect of Azacitidine and Sorafenib in treatment of a case of myeloid neoplasm with sole chromosomal abnormality t(8;22)(p11.2;q11.2)/BCR-FGFR1 rearrangement. | 0 |
| 21628071 | 2011 | t(8;22)/BCR-FGFR1 myeloproliferative disorder presenting as B-acute lymphoblastic leukemia: report of a case treated with sorafenib and review of the literature. | 0 |
| 11739186 | 2001 | The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins. | 0 |
| 30087462 | 2019 | Allogeneic hematopoietic stem cell transplantation for 8p11 myeloproliferative syndrome with BCR-FGFR1 gene rearrangement: a case report and literature review. | 0 |
| 31524018 | 2020 | Leukemic lineage switch in a t(8;22)(p11.2;q11.2)/BCR-FGFR1-rearranged myeloid/lymphoid neoplasm with RUNX1 mutation - diagnostic pitfalls and clinical management including FGFR1 inhibitor pemigatinib. | 0 |
| 28881484 | 2017 | Primary cells in BCR/FGFR1-positive 8p11 myeloproliferative syndrome are sensitive to dovitinib, ponatinib, and dasatinib. | 0 |
| 21239058 | 2011 | 8p11 Myeloproliferative syndrome with BCR-FGFR1 rearrangement presenting with T-lymphoblastic lymphoma and bone marrow stromal cell proliferation: a case report and review of the literature. | 0 |
| 20554971 | 2010 | Modeling the human 8p11-myeloproliferative syndrome in immunodeficient mice. | 0 |
| 34493159 | 2021 | A case of a patient characterized by t(8;22)(p11;q11) and BCR/FGFR1 fusion gene, who was successfully treated with haploidentical hematopoietic stem cell transplantation. | 0 |
| 30439482 | 2019 | Distinct signaling programs associated with progression of FGFR1 driven leukemia in a mouse model of stem cell leukemia lymphoma syndrome. | 0 |
| 27283163 | 2016 | Cytogenetic Evolution Associated With Disease Progression in Hematopoietic Neoplasms With t(8;22)(p11;q11)/BCR-FGFR1 Rearrangement. | 0 |
| 23171834 | 2013 | A case of 8p11 myeloproliferative syndrome with BCR-FGFR1 gene fusion presenting with trilineage acute leukemia/lymphoma, successfully treated by cord blood transplantation. | 0 |
| 20594995 | 2010 | B-cell acute lymphoblastic leukemia as evolution of a 8p11 myeloproliferative syndrome with t(8;22)(p11;q11) and BCR-FGFR1 fusion gene. | 0 |
| 17394134 | 2007 | Fusion gene-mediated truncation of RUNX1 as a potential mechanism underlying disease progression in the 8p11 myeloproliferative syndrome. | 0 |
| 17698633 | 2007 | Activity of TKI258 against primary cells and cell lines with FGFR1 fusion genes associated with the 8p11 myeloproliferative syndrome. | 0 |
| 33789375 | 2021 | [Application of transcriptome sequencing and fusion genes analysis in the diagnosis of myeloid leukemia with normal karyotype]. | 0 |
| 22106025 | 2012 | Favorable outcome of allogeneic hematopoietic cell transplantation for 8p11 myeloproliferative syndrome associated with BCR-FGFR1 gene fusion. | 0 |
| 23328683 | 2013 | Acute leukemia showing t(8;22)(p11;q11), myelodysplasia, CD13/CD33/CD19 expression and immunoglobulin heavy chain gene rearrangement. | 0 |
| 12522455 | 2002 | A fourth case of BCR-FGFR1 positive CML-like disease with t(8;22) translocation showing an extensive deletion on the derivative chromosome 8p. | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 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 |
| 11746971 | 2001 | 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. | Fioretos T et al |
Summary
Fusion gene
BCR/FGFR1 BCR (22q11.23) FGFR1 (8p11.23) M t(8;22)(p11;q11)|BCR/FGFR1 BCR (22q11.23) FGFR1 (8p11.23) TIC
it(8;22)(p11;q11) G- banding - Courtesy Jean-Luc Lai (left), Courtesy Diane H Norback, Eric B Johnson, and Sara Morrison-Delap, UW Cytogenetic Services (right).
Citation
Nicholas C P Cross
t(8;22)(p11;q11) BCR/FGFR1
Atlas Genet Cytogenet Oncol Haematol. 2002-01-01
Online version: http://atlasgeneticsoncology.org/haematological/1224/t(8;22)(p11;q11)-bcr-fgfr1
