8p11 myeloproliferative syndrome (FGFR1)

2010-12-01   José Luis Vizmanos , Paula Aranaz 

1.Department of Genetics, School of Sciences, University of Navarra, E-31008 Pamplona, Spain

Clinics and Pathology

Disease

Clinical entity defined by the disruption of the FGFR1 gene located at 8p11 with generation of a fusion gene between the 3 part of FGFR1 and the 5 part of the partner gene that also provides its promoter. The partner gene is always expressed in the haematopietic system and codes for a protein with oligomerization domains. As a result of oligomerization, chimeric proteins show constitutive and ligand-independent activation of FGFR1 kinase activity.
The 8p11 myeloproliferative syndrome (EMS) is a myeloproliferative disease with multilineage involvement characterized by chronic myelomonocytic leukemia (CMML)-like myeloid hyperplasia, marked peripheral blood eosinophilia and associated with a high incidence of non-Hodgkins lymphoma, usually of the T-cell lymphoblastic subtype. Occasional cases also show a B-cell lymphoproliferative disorder (Macdonald et al., 2002).
EMS cases were already described in the 1970s and 1980s, but cytogenetic and molecular analyses were not available (Manthorpe et al., 1977; Kjeldsberg et al., 1979; Catovsky et al., 1980; Posner et al., 1982). In 1992, 3 cases of T-cell lymphoblastic lymphoma associated with eosinophilia that subsequently developed acute myeloid leukemia or myelodysplastic/myeloproliferative neoplasms were reported (Abruzzo et al., 1992). One of them showed a t(8;13) by conventional cytogenetics. Later it was shown that one of the breakpoints involved one 8p11 locus (Xiao et al., 1998). In the same year, Rao et al. reported a patient with t(8;13)(p11;q12) who presented with leukocytosis, monocytosis, myeloid hyperplasia of bone marrow, and generalized lymphadenopathy due to T-cell lymphoblastic lymphoma (Rao et al., 1998). The term 8p11 myeloproliferative syndrome was suggested in 1995 by Macdonald et al. (Aguiar et al., 1995; Macdonald et al., 1995) and confirmed as clinical entity (SCLL) by Inhorn et al. (Inhorn et al., 1995).

Phenotype stem cell origin

The presence of the cytogenetic aberration in 8p11 both in myeloid and lymphoid cells, suggest a bilineage differentiation from a pluripotent and common stem cell (Macdonald et al., 2002).

Etiology

The FGFR1 fusion proteins that result from chromosomal translocations affecting 8p11 have constitutive and ligand-independent FGFR1 enzymatic activity. FGFR1 is a receptor tyrosine kinase that dimerizes upon ligand binding, activating multiple signalling pathways like Ras/MAPK, PI3K, PLCgamma and STAT. These pathways could be abnormally activated as consequence of FGFR1 aberration (Macdonald et al., 2002) resulting in cell transformation. In fact, expression of ZMYM2-FGFR1 and BCR-FGFR1 fusions in immunodeficient mice are capable of initiating an EMS-like disease (Agerstam et al., 2010). Different fusion proteins could activate these pathways in a different way and could explain the phenotypic variability of the disease (Roumiantsev et al., 2004; Cross and Reiter, 2008; Jackson et al., 2010).

Epidemiology

This is a very rare disease with less than 100 patients reported around the world and it can be found at any age. It has been reported at ages ranging from 3 to 84 years (median: 44 years). There is a slightly male-to-female predominance (Macdonald et al., 2002; Jackson et al., 2010).

Clinics

Around 20-25% of patients show systemic and unspecific symptoms like fatigue, night sweats, weight loss and fever and around 20% are asymptomatic (and the disease is detected in routine analyses). Near two thirds of patients show lymphadenopathy, generalized or localized. Hepato- and/or splenomegaly are also frequent events in these patients. One of the distinctive features of this disease is the high frequency of lymphoblastic lymphoma, uncommon in other myeloproliferative neoplasms (Macdonald et al., 2002; Jackson et al., 2010).

Cytology

It seems that neoplastic cells present in lymph nodes are predominantly small or medium lymphoblasts with a small cytoplasm (Jackson et al., 2010).

Pathology

The blood counts reported are variable. More than 90% of patients have leukocytosis and less than 10% have leukopenia but some cases have been reported with normal leukocyte counts. Eosinophilia is frequent, but monocytosis appears only in one third of patients. Basophils are increased only in cases with the t(8;22)(p11;q11). Blasts have been detected in half of the patients and some cases show blast counts typical of an acute leukemia. These blasts are mainly of a myeloid or myeloid and lymphoid (bilineal) lineage although some of them are also of an immature lymphoid lineage.
Most of the patients show a hypercellular bone marrow that leads to a diagnosis of myeloid hyperplasia or a myeloproliferative neoplasm. But in some cases, the dysplastic features lead to a diagnosis of myelodysplastic syndrome or a myelodisplastic syndrome/myeloproliferative neoplasm.
Most of the cases with lymph node biopsies reported had T-lymphoblastic lymphoma and the rest had myeloid sarcoma. In some cases evidence of bilineal T-cell/myeloid or B-and T- cell lymphoblastic lymphoma has been reported. For a review see Jackson et al., 2010.

Treatment

This is a very aggressive disease with a high rate of progression to an AML resistant to conventional chemotherapy with a median survival time of less than 12 months (Macdonald et al., 2002; Cross and Reiter, 2008; Jackson, 2010).
There are very few cases (Martinez-Climent et al., 1998; Zhou et al., 2010) responding to interferon alpha, this treatment could be useful at early stages. However, to date, only stem cell transplant remains effective to eradicate or suppress the malignant clone (Macdonald et al., 2002; Jackson et al., 2010). Median survival time for patients who received transplant after transformation to AML is 24 months (range 6-46 months) but median survival time is 12 months for the patients who did not received transplant (range 0-60 months) (Jackson et al., 2010). Currently there are no specific inhibitors for clinical use effective in this disease. Patients with FGFR1 fusions do not respond to drugs developed for other tyrosine kinases like imatinib, although several FGFR1 inhibitors have been tested, some of them with promising effects (Zhang et al., 2010; Zhou et al., 2010; Bhide et al., 2010; Risuleo et al., 2009; Ma et al., 2008; Cai et al., 2008; Chase et al., 2007; Kammasud et al., 2007; Klenke et al., 2007; Chen et al., 2004; Aviezier et al., 2000).

Evolution

This disease has a chronic phase characterized by myeloid hyperplasia and overproduction of myeloid cells that can differentiate, but without treatment the disease progresses rapidly (1 to 2 years after diagnosis) to an acute myeloid leukemia (AML) or sometimes to a B-lineage ALL (Macdonald et al., 1995; Inhorn et al., 1995; Macdonald et al., 2002; Jackson et al., 2010).
Gain of an additional copy of chromosome 21 is a non-random cytogenetic event apparently associated with progression of this disease (Agerstam et al., 2007; Goradia et al., 2008) but its role remains unclear (Jackson et al., 2010). This abnormality is reported in only 5 of 47 (10.6%) karyotypes at the time of diagnosis but in 10 of 13 (76.9%) karyotypes reported in follow-up. These karyotypes were mostly derived during clinical deterioration. In addition, some findings at the time of transformation from EMS to acute leukemia include the addition of various marker chromosomes, as well as trisomy of chromosomes 8, 9, 12 or 19 and deletions of chromosome 7 or either the 7p or 7q arms, and derivative chromosome 9 (Jackson et al., 2010).

Prognosis

As mentioned before, this is a devastating disease, which transforms to acute leukemia in a few months if left untreated, and in which the malignant clone cannot be eradicated by conventional chemotherapy. So at this moment, without specific FGFR1 inhibitors for clinical use, the stem cell transplant remains as the only possibility to a long-term survival (Macdonald et al., 1995; Inhorn et al., 1995; Macdonald et al., 2002; Jackson et al., 2010).

Note

This disease is defined by the fusion of FGFR1 (8p11) with other partner genes, as consequence of a cytogenetic aberration, mainly chromosomal translocations. FGFR1 codes for a receptor tyrosine kinase. The gene fusion maintains the 3 terminal part of the FGFR1 gene (from exon 9) joined to the 5 terminal part of the partner gene. Partner genes are widely expressed and fusion genes have also this expression pattern. The chimeric gene codes for a protein which retains the TK domain from FGFR1 and oligomerization domains provided by the partner gene. This protein has a constitutive and ligand-independent activity and activates multiple signal transduction pathways.This disease is related to fusion genes between FGFR1, located in 8p11, and several partner genes. However there are some other aberrations affecting this chromosomal band and 8p12 in other neoplasms. Some acute myeloid leukemia (AML) cases have been described related to translocations affecting MYST3 (also known as MOZ) (Borrow et al., 1996; Carapeti et al., 1998; Chaffanet et al., 2000; Murati et al., 2007; Esteyries et al., 2008; Gervais et al., 2008) and WHSC1L1 (also known as NSD3) (Rosati et al., 2002; Romana et al., 2006; Taketani et al., 2009), both of them in 8p11. In addition, aberrations in 8p11-p12 are also frequent events in breast cancer, but the loci responsible are not well known (Yang et al., 2004; Garcia et al., 2005; Gelsi-Boyer et al., 2005; Pole et al., 2006; Yang et al., 2006; Yang et al., 2010).

Genes Involved and Proteins

Gene name
ZMYM2 (fused in myeloproliferative disorders).
Location
13q12.11
Protein description
ZMYM2 (also known as ZNF198, RAMP -rearranged in atypical myeloproliferative disorder-, or FIM - fused in myeloproliferative disorder) codes for a zinc finger protein that may act as a transcription factor involved in ribosomal RNA transcription and also could be part of a BHC histone deacetylase complex. The chimeric protein retains the proline-rich domain of ZMYM2 (an oligomerization domain) and the tyrosine kinase domain of FGFR1. The abnormal oligomerization of the chimeric protein leads to constitutive and ligand-independent activation. In addition, this abnormal protein is located in the cytoplasm and not in the membrane as native FGFR1. , Recently, MYO18A has also been found fused to PDGFRB as consequence of a t(5;17)(q33-q34;q11) but with a different breakpoint in which all the predicted coiled-coil domains of normal MYO18A are retained in the chimeric protein (Walz et al., 2009).
Gene name
FGFR1OP (FGFR1 oncogene partner)
Location
6q27
Protein description
FGFR1OP, widely expressed, codes for a hydrophilic centrosomal protein that could be a member of a leucine-rich protein family, and it is involved in the anchoring of microtubules (MTS) to subcellular structures. FGFR1OP could play a role in lung cancer growth and progression and has been proposed as a prognostic biomarker for this disease (Mano et al., 2007).
Gene name
CNTRL (centriolin)
Location
9q33.2
Protein description
CEP110 encodes also a centrosomal protein with several leucine zipper motifs required for the centrosome to function as a microtubule organizing center. CEP110 is also widely expressed and CEP110-FGFR1 retains the leucine zipper motifs of CEP110 at its N-terminus which could mediate the consititutive activation of the FGFR1 catalytic domain at its C-terminus. In addition the CEP110-FGFR1 fusion protein has been found in the cytoplasm, whereas both CEP110 and FGFR1 wild-type proteins are centrosome and plasma membrane-bound proteins respectively (Guasch et al., 2000).
Gene name
BCR (Breakpoint cluster region)
Location
22q11.23
Protein description
BCR is, like ETV6, a common fusion partner of several tyrosine kinase genes rearranged in myeloid disorders (BCR-ABL, BCR-JAK2, BCR-PDGFRA and BCR-FGFR1 have been described to date). However function of the protein encoded by this gene is not clear and its name comes from breakpoint cluster region.
Gene name
NUP98 (nucleoporin 98 kDa)
Location
11p15.4
Gene name
ERVK-6 (endogenous retrovirus group K member 6, envelope)
Location
7p22.1
Protein description
HERV-K is also ubiquitously expressed. The HERV-Ks are human specific endogenous retrovirus that have been proposed as etiological cofactors in some chronic diseases like cancer because they are mobile elements that could disrupt tumor suppressor and/or DNA repair genes. In this case, it seems that the part of the HERV-K sequence fused showed similarities with a retroviral envelope protein whose dimerization would induce the constitutive activation of the chimeric protein HERVK-FGFR1 (Guasch et al., 2003).
Gene name
FGFR1OP2 (FGFR1 oncogene partner 2)
Location
12p11.23
Protein description
As other FGFR1 partners, FGFR1OP2 is also widely expressed but its function is unknown. It could code for a cytoskeleton molecule (Lin et al., 2010). However, the putative protein coded by this gene has four potential coiled-coil domains and the first two are retained in the chimeric protein, so they could mediate its oligomerization and constitutive activation (Grand et al., 2004).
Gene name
TRIM24 (tripartite motif-containing 24)
Location
7q33
Protein description
TRIM24 (previously known as TIF1) codes for a protein of the tripartite motif (TRIM) family that mediates transcriptional control by interaction with several nuclear receptors and localizes to nuclear bodies. The tripartite motif includes three zinc-binding domains - a RING, a B-box type 1 and a B-box type 2 - and a coiled-coil region that is retained in the chimeric protein so it could promote, as other FGFR1 fusion proteins, its constitutive and ligand-independent activation
Gene name
MYO18A (myosin XVIIIA)
Location
17q11.2
Protein description
MYO18A is a widely expressed gene that codes for a protein of unknown function of the myosin superfamily. It has been recently described that this protein is a novel PAK2 (p21-activated kinase 2) binding partner (Hsu et al., 2010). PAK2 has many biological functions, including the regulation of actin reorganization and cell motility. MYO18A contains several functional motifs that are retained in MYO18A-FGFR1, including an N-terminal PDZ (PSD-95/Dlg/ZO-1) protein-protein interaction domain, a myosin head domain and a region that is predicted to form multiple coiled-coils. Some of these coiled-coils could drive oligomerization of MYO18A-FGFR1, with consequent constitutive activation of the FGFR1 kinase activity.
Gene name
CPSF6 (cleavage and polyadenylation specific factor 6)
Location
12q15
Protein description
The protein encoded by CPSF6 is the 68 kD subunit of a cleavage factor required for 3 RNA cleavage and polyadenylation processing. Unlike other partners of FGFR1, CPSF6 does not have any identifiable oligomerisation motifs. However RNA recognition motifs (RRM) such as the one retained in CPSF6-FGFR1, could mediate the dimerization needed for constitutive activation of the CPSF6-FGFR1 kinase activity.
Gene name
LRRFIP1 (LRR binding FLII interacting protein 1)
Location
2q37.3
Protein description
LRRFIP1 (Leucine-rich repeat Flightless-Interacting Protein 1) is a ubiquitously expressed gene that encodes for a nuclear and cytoplasmatic protein with multiple functions. In the nucleus, it acts as a transcriptional repressor that decreases the expression of EGFR, PDGFRA and TNF. In the cytoplasm, it interacts with actin-binding proteins. It has an N-terminal coiled-coil domain that, as other FGFR1 partners, could drive the dimerization of LRRFIP1-FGFR1 leading to the constitutive activation of the kinase activity.

Result of the Chromosomal Anomaly

Detection protocole

Methods of detection
1. Conventional cytogenetics to identify translocations or other rearrangements involving 8p11.
2. Fluorescent in situ hibridization (FISH) with probes flanking or covering FGFR1 to demonstrate disruption of this gene.
3. 5 RACE PCR to identify FGFR1 partner gene.
4. RT-PCR with primers located in both genes fused.

Bibliography

Pubmed IDLast YearTitleAuthors
15990151992T-cell lymphoblastic lymphoma with eosinophilia associated with subsequent myeloid malignancy.Abruzzo LV et al
205549712010Modeling the human 8p11-myeloproliferative syndrome in immunodeficient mice.Agerstam H et al
108504452000Porphyrin analogues as novel antagonists of fibroblast growth factor and vascular endothelial growth factor receptor binding that inhibit endothelial cell proliferation, tumor progression, and metastasis.Aviezer D et al
205949952010B-cell acute lymphoblastic leukemia as evolution of a 8p11 myeloproliferative syndrome with t(8;22)(p11;q11) and BCR-FGFR1 fusion gene.Baldazzi C et al
1560934220058p11 myeloproliferative syndrome with a novel t(7;8) translocation leading to fusion of the FGFR1 and TIF1 genes.Belloni E et al
201036042010The antiangiogenic activity in xenograft models of brivanib, a dual inhibitor of vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1 kinases.Bhide RS et al
87828171996The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein.Borrow J et al
182887932008Discovery of brivanib alaninate ((S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-yl)2-aminopropanoate), a novel prodrug of dual vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1 kinase inhibitor (BMS-540215).Cai ZW et al
95583661998A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in acute myeloid leukemia.Carapeti M et al
69329541980The association of eosinophilia with lymphoblastic leukaemia or lymphoma: a study of seven patients.Catovsky D et al
108249982000MOZ is fused to p300 in an acute monocytic leukemia with t(8;22).Chaffanet M et al
176986332007Activity of TKI258 against primary cells and cell lines with FGFR1 fusion genes associated with the 8p11 myeloproliferative syndrome.Chase A et al
154482052004PKC412 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
185665372008Fibroblast growth factor receptor and platelet-derived growth factor receptor abnormalities in eosinophilic myeloproliferative disorders.Cross NC et al
117391862001The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins.Demiroglu A et al
178053312008NCOA3, a new fusion partner for MOZ/MYST3 in M5 acute myeloid leukemia.Esteyries S et al
117469712001Fusion 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
158978722005A 1 Mb minimal amplicon at 8p11-12 in breast cancer identifies new candidate oncogenes.Garcia MJ et al
163805032005Comprehensive profiling of 8p11-12 amplification in breast cancer.Gelsi-Boyer V et al
185284282008Acute myeloid leukaemia with 8p11 (MYST3) rearrangement: an integrated cytologic, cytogenetic and molecular study by the groupe francophone de cytogénétique hématologique.Gervais C et al
187876272008The 8p11 myeloproliferative syndrome: review of literature and an illustrative case report.Goradia A et al
150348732004Identification of a novel gene, FGFR1OP2, fused to FGFR1 in 8p11 myeloproliferative syndrome.Grand EK et al
169463002006Phosphotyrosine profiling identifies the KG-1 cell line as a model for the study of FGFR1 fusions in acute myeloid leukemia.Gu TL et al
106888392000FGFR1 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
123935972003Endogenous 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
182052092008The 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
199233222010Identification of MYO18A as a novel interacting partner of the PAK2/betaPIX/GIT1 complex and its potential function in modulating epithelial cell migration.Hsu RM et al
76619401995A syndrome of lymphoblastic lymphoma, eosinophilia, and myeloid hyperplasia/malignancy associated with t(8;13)(p11;q11): description of a distinctive clinicopathologic entity.Inhorn RC et al
2022696220108p11 myeloproliferative syndrome: a review.Jackson CC et al
176181132007Novel inhibitor for fibroblast growth factor receptor tyrosine kinase.Kammasud N et al
3894131979Acute myeloblastic leukemia developing in patients with mediastinal lymphoblastic lymphoma.Kjeldsberg CR et al
173675412007Tyrosine kinase inhibitor SU6668 represses chondrosarcoma growth via antiangiogenesis in vivo.Klenke FM et al
3066821978Acute myelogenous leukemia: a human cell line responsive to colony-stimulating activity.Koeffler HP et al
66272221983The predictive value of initial cytogenetic studies in 148 adults with acute nonlymphocytic leukemia: a 12-year study (1970-1982).Larson RA et al
199598142010Small cytoskeleton-associated molecule, fibroblast growth factor receptor 1 oncogene partner 2/wound inducible transcript-3.0 (FGFR1OP2/wit3.0), facilitates fibroblast-driven wound closure.Lin A et al
190206612008The marine-derived oligosaccharide sulfate (MdOS), a novel multiple tyrosine kinase inhibitor, combats tumor angiogenesis both in vitro and in vivo.Ma J et al
119193912002The 8p11 myeloproliferative syndrome: a distinct clinical entity caused by constitutive activation of FGFR1.Macdonald D et al
178880342007Fibroblast growth factor receptor 1 oncogene partner as a novel prognostic biomarker and therapeutic target for lung cancer.Mano Y et al
1417281977A case of T-cell lymphoma with Sézary cells in the blood and bone marrow accompanied by peripheral T and B lymphocytosis.Manthorpe R et al
96394341998Cytogenetic response induced by interferon alpha in the myeloproliferative disorder with eosinophilia, T cell lymphoma and the chromosomal translocation t(8;13)(p11;q12)Martinez-Climent JA et al
180962252008Common features of myeloproliferative disorders with t(8;9)(p12;q33) and CEP110-FGFR1 fusion: report of a new case and review of the literature.Mozziconacci MJ et al
111221152000The 8p12 myeloproliferative disorder. t(8;19)(p12;q13.3): a novel translocation involving the FGFR1 gene.Mugneret F et al
172965832007New types of MYST3-CBP and CBP-MYST3 fusion transcripts in t(8;16)(p11;p13) acute myeloid leukemias.Murati A et al
166366682006High-resolution analysis of chromosome rearrangements on 8p in breast, colon and pancreatic cancer reveals a complex pattern of loss, gain and translocation.Pole JC et al
99491821999The 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
69793791982T-cell lymphoblastic lymphoma with subsequent acute nonlymphocytic leukemia: a case report.Posner MR et al
12923101992Cytogenetic evidence for extramedullary blast crisis with t(8;13)(q11;p11) in chronic myelomonocytic leukemia.Rao PH et al
97166031998Consistent fusion of ZNF198 to the fibroblast growth factor receptor-1 in the t(8;13)(p11;q12) myeloproliferative syndrome.Reiter A et al
200033432009The synthetic inhibitor of fibroblast growth factor receptor PD166866 controls negatively the growth of tumor cells in culture.Risuleo G et al
164678682006NUP98 rearrangements in hematopoietic malignancies: a study of the Groupe Francophone de Cytogénétique Hématologique.Romana SP et al
119862492002NUP98 is fused to the NSD3 gene in acute myeloid leukemia associated with t(8;11)(p11.2;p15).Rosati R et al
150509202004Distinct stem cell myeloproliferative/T lymphoma syndromes induced by ZNF198-FGFR1 and BCR-FGFR1 fusion genes from 8p11 translocations.Roumiantsev S et al
94994161998The 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.Smedley D et al
115502832001Identification of four new translocations involving FGFR1 in myeloid disorders.Sohal J et al
193699592009LRRFIP1, a new FGFR1 partner gene associated with 8p11 myeloproliferative syndrome.Soler G et al
193800292009NUP98-NSD3 fusion gene in radiation-associated myelodysplastic syndrome with t(8;11)(p11;p15) and expression pattern of NSD family genes.Taketani T et al
194723962009The 2008 World Health Organization classification system for myeloproliferative neoplasms: order out of chaos.Tefferi A et al
178822802008Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms.Tefferi A et al
155702992004Clinical variability of patients with the t(6;8)(q27;p12) and FGFR1OP-FGFR1 fusion: two further cases.Vizmanos JL et al
158006732005The t(8;17)(p11;q23) in the 8p11 myeloproliferative syndrome fuses MYO18A to FGFR1.Walz C et al
190060782009Identification of a MYO18A-PDGFRB fusion gene in an eosinophilia-associated atypical myeloproliferative neoplasm with a t(5;17)(q33-34;q11.2).Walz C et al
94259081998FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome.Xiao S et al
155279032004Genomic organization of the 8p11-p12 amplicon in three breast cancer cell lines.Yang ZQ et al
209404042010Transforming properties of 8p11-12 amplified genes in human breast cancer.Yang ZQ et al
171788572006Multiple interacting oncogenes on the 8p11-p12 amplicon in human breast cancer.Yang ZQ et al
210802102012A new diaryl urea compound, D181, induces cell cycle arrest in the G1 and M phases by targeting receptor tyrosine kinases and the microtubule skeleton.Zhang J et al
206505282010Complete molecular remission after interferon alpha treatment in a case of 8p11 myeloproliferative syndrome.Zhou L et al
203385202010A structure-guided approach to creating covalent FGFR inhibitors.Zhou W et al

Summary

Note

Although "8p11 myeloproliferative syndrome" (EMS) (Macdonald et al., 1995) is the most frequent name for this disease in the literature, it must be designated as "myeloid and lymphoid neoplasm with FGFR1 abnormalities" under the current 2008 World Health Organization classification (Tefferi and Vardiman, 2008; Tefferi et al., 2009). This disease has been referred to as "stem cell leukemia/lymphoma" (SCLL) (Inhorn et al., 1995) which remark the coexistence of lymphoma, myeloid malignancy and lymphoblastic leukemia.

Citation

José Luis Vizmanos ; Paula Aranaz

8p11 myeloproliferative syndrome (FGFR1)

Atlas Genet Cytogenet Oncol Haematol. 2010-12-01

Online version: http://atlasgeneticsoncology.org/haematological/1091/8p11-myeloproliferative-syndrome-(fgfr1)