Difference between revisions of "Myeloid/Lymphoid Neoplasms with PDGFRB Rearrangement"

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==Primary Author(s)*==
 
==Primary Author(s)*==
  
Daynna J.Wolff
+
Christopher Sullivan, MD, MPH and Daynna J. Wolff, PhD
  
 
__TOC__
 
__TOC__
Line 8: Line 8:
 
==Cancer Category/Type==
 
==Cancer Category/Type==
  
Put your text here
+
Myeloid Neoplasms/Acute myeloid leukemia
  
 
==Cancer Sub-Classification / Subtype==
 
==Cancer Sub-Classification / Subtype==
  
Put your text here
+
Myeloid/Lymphoid Neoplasms with PDGFRB Rearrangement
  
 
==Definition / Description of Disease==
 
==Definition / Description of Disease==
 
+
Gene fusions with PDGFRB were first described by Golub et al. in 1994 in a patient with features consistent with chronic myelomonocytic leukemia (CMML)<ref>Golub TR, Barker GF, Lovett M, Gilliland DG. Fusion of PDGF receptor-beta to a novel Ets-like gene, Tel, in chronic myelomonocytic leukemia with t(512) chromosomal translocation. Cell. 1994;77(2):307–16.</ref>. Since that time, over 20 fusion partners have been described<ref>Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, Kutok J, Clark J, Galinsky I, et al. 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.</ref><ref name=":0">Vega F, Medeiros LJ, Bueso-Ramos CE, Arboleda P, Miranda RN. Hematolymphoid neoplasms associated with rearrangements of PDGFRA, PDGFRB, and FGFR1. Am J Clin Pathol. 2015;144(3):377–92.</ref>. Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRB are rare, accounting for less than 2% of all myelodysplastic/myeloproliferative neoplasms (MDS/MPN)<ref name=":0" />.
Put your text here
 
  
 
==Synonyms / Terminology==
 
==Synonyms / Terminology==
  
Put your text here
+
Chronic myelomonocytic leukemia with eosinophilia associated with t(5;12); myeloid neoplasms with PDGFRB rearrangement; myeloid neoplasms associated with PDGFRB rearrangement.
  
 
==Epidemiology / Prevalence==
 
==Epidemiology / Prevalence==
  
Put your text here
+
This neoplasm is considerably more common in men than in women (male-to-female ratio: 2:1) and occurs over a wide age range (8-72 years), with peak incidence in middle-aged adults and a median age of onset in the late 40s<ref name=":1">Steer, E. J., & Cross, N. C. (2002). Myeloproliferative disorders with translocations of chromosome 5q31–35: role of the platelet-derived growth factor receptor Beta. ''Acta haematologica'', ''107''(2), 113-122.</ref>.
  
 
==Clinical Features==
 
==Clinical Features==
 
+
Patients typically present with splenomegaly; hepatomegaly is less frequent. Lymphadenopathy may also be seen. Skin and cardiac infiltration may be present at diagnosis with resulting cardiac damage. Serum tryptase levels may be elevated.
Put your text here
 
  
 
==Sites of Involvement==
 
==Sites of Involvement==
  
Put your text here
+
MPN associated with t(5;12)(q32;p13.2) is a multisystem disorder. The peripheral blood and bone marrow are always involved. The spleen is enlarged in most cases. Tissue infiltration by eosinophils and cytokine release, humoral factors, or granule contents by eosinophils can contribute to tissue damage in several organs<ref name=":2">Swerdlow SH, Campo E, Harris NL, et al.  WHO classification of tumours of haematopoietic and lymphoid tissues. In: Bosman FT, Jaffe ES, Lakhani SR, Ohgaki H, eds. World Health Organization Classification of Tumours. Lyon, France: IARC; 2008</ref>.
  
 
==Morphologic Features==
 
==Morphologic Features==
 +
In patients with abnormalities of PDGFRB, peripheral blood and bone marrow is almost always involved. Leukocytosis is typical with monocytosis and eosinophilia. Rarely, basophilia is also prominent. Anemia and thrombocytopenia may also be present. Overall, the features are typically suggestive of CMML with eosinophilia; however, some patients present with features more in keeping with aCML or CEL. Rarely, they present with features of ALL, AML, and juvenile myelomonocytic leukemia (JMML)<ref>Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, Kutok J, Clark J, Galinsky I, et al. 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.</ref>.
  
Put your text here
+
==Immunophenotype==
  
==Immunophenotype==
+
The mast cells show expression of CD2 and CD25, which is also found in most mast cell disease.
  
Put your text here and/or fill in the table
+
==Chromosomal Rearrangements (Gene Fusions)==
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
!Finding!!Marker
+
!Translocation!!Fusion Gene!!Hematological Diagnosis
 +
|-
 +
|t(5;12)(q32;p13.2)
 +
|ETV6-PDGFRB
 +
|CMML with eosinophilia, CEL
 +
|-
 +
|t(1;3;5)(q36;q11.2)||WDR48-PDGFRB||CEL
 +
|-
 +
|der(1)t(1;5)(p34;q32),
 +
der(5)t(1;5)(p34;q15),
 +
 
 +
der(11)ins(11;5)(p13;q15q32)
 +
|CAPRIN1-PDGFRB||CEL
 +
|-
 +
|t(1;5)(q21.3;q32)
 +
|TPM3-PDGFRB
 +
|
 
|-
 
|-
|Positive (universal)||EXAMPLE CD1
+
|t(1;5)(q21.2;q32)
 +
|PDE4DIP-PDGFRB
 +
|MDS/MPN with eosinophilia
 
|-
 
|-
|Positive (subset)||EXAMPLE CD2
+
|t(2;5)(p16.2;q32)
 +
|SPTBN1-PDGFRB
 +
|
 
|-
 
|-
|Negative (universal)||EXAMPLE CD3
+
|t(4;5;5)(q21.2;q31;q32)
 +
|PRKG2-PDGFRB
 +
|Chronic basophilia leukemia
 
|-
 
|-
|Negative (subset)||EXAMPLE CD4
+
|t(3;5)(p22.2;q32)
|}
+
|GOLGA4-PDGFRB
 
+
|CEL or aCML with eosinophilia
==Chromosomal Rearrangements (Gene Fusions)==
+
|-
 
+
|Cryptic interstitial deletion of 5q
Put your text here and/or fill in the table
+
|TNIP1-PDGFRB
 
+
|CEL with thrombocytosis
{| class="wikitable sortable"
+
|-
 +
|t(5;7)(q32;q11.2)
 +
|HIP1-PDGFRB
 +
|CMML with eosinophilia
 +
|-
 +
|t(5;7)(q32;p14.1)
 +
|HECW1-PDGFRB
 +
|JMML
 +
|-
 +
|t(5;9)(q32;p24.3)
 +
|KANK1-PDGFRB
 +
|Essential thrombocythemia without eosinophilia
 +
|-
 +
|t(5;10)(q32;q21.2)
 +
|CCDC6-PDGFRB
 +
|aCML with eosinophilia or MPN with eosinophilia
 +
|-
 +
|Uninformative
 +
|SART3-PDGFRB
 +
|MPN with eosniophilia
 
|-
 
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
+
|t(5;12)(q32;q24.1)
 +
|GIT2-PDGFRB
 +
|CEL
 
|-
 
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 5%
+
|t(5;12)(q32;p13.3)
 +
|ERC1-PDGFRB
 +
|AML without eosniophilia
 
|-
 
|-
|EXAMPLE t(8;21)(q22;q22)||EXAMPLE 5'RUNX1 / 3'RUNXT1||EXAMPLE der(8)||EXAMPLE 5%
+
|t(5;12)(q32;p13.1)
|}
+
|BIN2-PDGFRB
+
|aCML with eosinophilia
==Characteristic Chromosomal Aberrations / Patterns==
 
 
 
Put your text here
 
 
 
==Genomic Gain/Loss/LOH==
 
 
 
Put your text here and/or fill in the table
 
 
 
{| class="wikitable sortable"
 
 
|-
 
|-
!Chromosome Number!!Gain/Loss/Amp/LOH!!Region
+
|t(5;14)(q32;q22.1)
 +
|NIN-PDGFRB
 +
|Ph-negative CML (13% eosinophils)
 
|-
 
|-
|EXAMPLE 8||EXAMPLE Gain||EXAMPLE chr8:0-1000000
+
|t(5;14)(q32;q32.1)
 +
|CCDC88C-PDGFRB
 +
|CMML with eosinophilia
 
|-
 
|-
|EXAMPLE 7||EXAMPLE Loss||EXAMPLE chr7:0-1000000
+
|t(5;15)(q32;q15.3)
|}
+
|TP53BP1-PDGFRB
+
|Ph-negative CML with prominent eosinophilia
==Gene Mutations (SNV/INDEL)==
 
 
 
Put your text here and/or fill in the tables
 
 
 
{| class="wikitable sortable"
 
 
|-
 
|-
!Gene!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)
+
|t(5;16)(q32;p13.1)
 +
|NDE1-PDGFRB
 +
|CMML
 
|-
 
|-
|EXAMPLE TP53||EXAMPLE R273H||EXAMPLE Tumor Suppressor||EXAMPLE LOF||EXAMPLE 20%
+
|t(5;17)(q32;p13.2)
|}
+
|RABEP1-PDGFRB
+
|CMML
===Other Mutations===
 
{| class="wikitable sortable"
 
 
|-
 
|-
!Type!!Gene/Region/Other
+
|t(5;17)(q32;p11.2)
 +
|SPECC1-PDGFRB
 +
|JMML
 
|-
 
|-
|Concomitant Mutations||EXAMPLE IDH1 R123H
+
|t(5;17)(q32;q11.2)
 +
|MYO18A-PDGFRB
 +
|MPN with eosinophilia
 
|-
 
|-
|Secondary Mutations||EXAMPLE Trisomy 7
+
|t(5;17)(q32;q21.3)
 +
|COL1A1-PDGFRB
 +
|MDS or MPN with eosinophilia
 
|-
 
|-
|Mutually Exclusive||EXAMPLE EGFR Amplification
+
|t(5;20)(q32;p11.2)
|}
+
|DTD1-PDGFRB
 
+
|CEL
==Epigenomics (Methylation)==
+
|}
 +
 +
==Characteristic Chromosomal Aberrations / Patterns==
  
Put your text here
+
t(5:12)(q32;p13.2), translocation resulting in ETV6-PDGFRB.
 +
==Gene Mutations==
 +
Fusion results in the joining of the N-terminal domain of ETV6 to the tyrosine kinase-containing C-terminal of PDGFRB. This leads to oligomerization at the pointed domain, constituently active phosphorylation, and activation of STAT proteins<ref>Chen J, Williams IR, Kutok JL, Duclos N, Anastasiadou E, Masters SC, et al. Positive and negative regulatory roles of the WW-like domain in TEL-PDGFbetaR transformation. Blood. 2004;104(2):535–42.</ref>.
  
 
==Genes and Main Pathways Involved==
 
==Genes and Main Pathways Involved==
 
+
PDGFRB encodes a plasma membrane-spanning receptor with five extracellular immunoglobulin-like loops for ligand binding and a split intracellular tyrosine kinase domain. Signal transduction is very similar, with ligand binding inducing dimerization and autophosphorylation of the tyrosine kinase. In addition to its role in embryonic development, PDGFRB mediates chemotactic responses of monocytes, macrophages, and platelets to inflammatory processes. Overexpression has been implicated in solid tumors, such as medulloblastoma and chordoma<ref>Chang, C. C., & Ohgami, R. S. (Eds.). (2018). ''Precision molecular pathology of myeloid neoplasms''. Springer.</ref>.
Put your text here
 
  
 
==Diagnostic Testing Methods==
 
==Diagnostic Testing Methods==
  
Put your text here
+
FISH (break-apart FISH with a PDGFRB probe) is indicated in all patients with a presumptive diagnosis of MPN with a 5q31-33 breakpoint, in particular if there is eosinophilia. However, FISH analysis does not always demonstrate rearrangement of PDGFRB even when such rearrangement is detectable on Southern blot anaylsis<ref name=":1" />. Molecular analysis is not indicated when no 5q31-33 breakpoint is found by conventional cytogenetic analysis, because almost all cases reported to date in which 20 metaphases were available for examination have had a cytogenetically detectable abnormality<ref name=":2" />.
  
 
==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==
 
==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==
  
Put your text here
+
Before the introduction of imatinib therapy, the median survival was <2 years. Most patients are now known to have excellent morphologic and molecular response to therapy with a recent study showing a 10-year overall survival of 90%<ref>Cheah CY, Burbury K, Apperley JF, Huguet F, Pitini V, Gardembas M, et al. Patients with myeloid malignancies bearing PDGFRB fusion genes achieve durable long-term remissions with imatinib. Blood. 2014;123(23):3574–7.</ref>. Furthermore, earlier diagnosis due to recognition of this entity will result in earlier initiation of appropriate therapy, preventing cardiac damage and blast phase. Primary and secondary resistance is uncommon; however, initial response typically occurs within 2 months, and if not seen by 3 months, consideration of another therapy is suggested. Whether or not therapy can be stopped in patients with long term molecular remission is still up for debate, with a recent article citing one patient in remission 4 years after therapy cessation<ref>Cerrano M, Crisà E, Gottardi E, Aguzzi C, Boccadoro M, Ferrero D. Long-term therapy-free remission in a patient with platelet-derived growth factor receptor beta (PDGFRB)- rearranged myeloproliferative neoplasm. Am J Hematol. 2016;91(9):E353.</ref>.
 
 
==Familial Forms==
 
 
 
Put your text here
 
 
 
==Other Information==
 
 
 
Put your text here
 
  
 
==Links==
 
==Links==
Line 137: Line 172:
  
 
==References==
 
==References==
 
+
<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.
 

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Primary Author(s)*

Christopher Sullivan, MD, MPH and Daynna J. Wolff, PhD

Cancer Category/Type

Myeloid Neoplasms/Acute myeloid leukemia

Cancer Sub-Classification / Subtype

Myeloid/Lymphoid Neoplasms with PDGFRB Rearrangement

Definition / Description of Disease

Gene fusions with PDGFRB were first described by Golub et al. in 1994 in a patient with features consistent with chronic myelomonocytic leukemia (CMML)[1]. Since that time, over 20 fusion partners have been described[2][3]. Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRB are rare, accounting for less than 2% of all myelodysplastic/myeloproliferative neoplasms (MDS/MPN)[3].

Synonyms / Terminology

Chronic myelomonocytic leukemia with eosinophilia associated with t(5;12); myeloid neoplasms with PDGFRB rearrangement; myeloid neoplasms associated with PDGFRB rearrangement.

Epidemiology / Prevalence

This neoplasm is considerably more common in men than in women (male-to-female ratio: 2:1) and occurs over a wide age range (8-72 years), with peak incidence in middle-aged adults and a median age of onset in the late 40s[4].

Clinical Features

Patients typically present with splenomegaly; hepatomegaly is less frequent. Lymphadenopathy may also be seen. Skin and cardiac infiltration may be present at diagnosis with resulting cardiac damage. Serum tryptase levels may be elevated.

Sites of Involvement

MPN associated with t(5;12)(q32;p13.2) is a multisystem disorder. The peripheral blood and bone marrow are always involved. The spleen is enlarged in most cases. Tissue infiltration by eosinophils and cytokine release, humoral factors, or granule contents by eosinophils can contribute to tissue damage in several organs[5].

Morphologic Features

In patients with abnormalities of PDGFRB, peripheral blood and bone marrow is almost always involved. Leukocytosis is typical with monocytosis and eosinophilia. Rarely, basophilia is also prominent. Anemia and thrombocytopenia may also be present. Overall, the features are typically suggestive of CMML with eosinophilia; however, some patients present with features more in keeping with aCML or CEL. Rarely, they present with features of ALL, AML, and juvenile myelomonocytic leukemia (JMML)[6].

Immunophenotype

The mast cells show expression of CD2 and CD25, which is also found in most mast cell disease.

Chromosomal Rearrangements (Gene Fusions)

Translocation Fusion Gene Hematological Diagnosis
t(5;12)(q32;p13.2) ETV6-PDGFRB CMML with eosinophilia, CEL
t(1;3;5)(q36;q11.2) WDR48-PDGFRB CEL
der(1)t(1;5)(p34;q32),

der(5)t(1;5)(p34;q15),

der(11)ins(11;5)(p13;q15q32)

CAPRIN1-PDGFRB CEL
t(1;5)(q21.3;q32) TPM3-PDGFRB
t(1;5)(q21.2;q32) PDE4DIP-PDGFRB MDS/MPN with eosinophilia
t(2;5)(p16.2;q32) SPTBN1-PDGFRB
t(4;5;5)(q21.2;q31;q32) PRKG2-PDGFRB Chronic basophilia leukemia
t(3;5)(p22.2;q32) GOLGA4-PDGFRB CEL or aCML with eosinophilia
Cryptic interstitial deletion of 5q TNIP1-PDGFRB CEL with thrombocytosis
t(5;7)(q32;q11.2) HIP1-PDGFRB CMML with eosinophilia
t(5;7)(q32;p14.1) HECW1-PDGFRB JMML
t(5;9)(q32;p24.3) KANK1-PDGFRB Essential thrombocythemia without eosinophilia
t(5;10)(q32;q21.2) CCDC6-PDGFRB aCML with eosinophilia or MPN with eosinophilia
Uninformative SART3-PDGFRB MPN with eosniophilia
t(5;12)(q32;q24.1) GIT2-PDGFRB CEL
t(5;12)(q32;p13.3) ERC1-PDGFRB AML without eosniophilia
t(5;12)(q32;p13.1) BIN2-PDGFRB aCML with eosinophilia
t(5;14)(q32;q22.1) NIN-PDGFRB Ph-negative CML (13% eosinophils)
t(5;14)(q32;q32.1) CCDC88C-PDGFRB CMML with eosinophilia
t(5;15)(q32;q15.3) TP53BP1-PDGFRB Ph-negative CML with prominent eosinophilia
t(5;16)(q32;p13.1) NDE1-PDGFRB CMML
t(5;17)(q32;p13.2) RABEP1-PDGFRB CMML
t(5;17)(q32;p11.2) SPECC1-PDGFRB JMML
t(5;17)(q32;q11.2) MYO18A-PDGFRB MPN with eosinophilia
t(5;17)(q32;q21.3) COL1A1-PDGFRB MDS or MPN with eosinophilia
t(5;20)(q32;p11.2) DTD1-PDGFRB CEL

Characteristic Chromosomal Aberrations / Patterns

t(5:12)(q32;p13.2), translocation resulting in ETV6-PDGFRB.

Gene Mutations

Fusion results in the joining of the N-terminal domain of ETV6 to the tyrosine kinase-containing C-terminal of PDGFRB. This leads to oligomerization at the pointed domain, constituently active phosphorylation, and activation of STAT proteins[7].

Genes and Main Pathways Involved

PDGFRB encodes a plasma membrane-spanning receptor with five extracellular immunoglobulin-like loops for ligand binding and a split intracellular tyrosine kinase domain. Signal transduction is very similar, with ligand binding inducing dimerization and autophosphorylation of the tyrosine kinase. In addition to its role in embryonic development, PDGFRB mediates chemotactic responses of monocytes, macrophages, and platelets to inflammatory processes. Overexpression has been implicated in solid tumors, such as medulloblastoma and chordoma[8].

Diagnostic Testing Methods

FISH (break-apart FISH with a PDGFRB probe) is indicated in all patients with a presumptive diagnosis of MPN with a 5q31-33 breakpoint, in particular if there is eosinophilia. However, FISH analysis does not always demonstrate rearrangement of PDGFRB even when such rearrangement is detectable on Southern blot anaylsis[4]. Molecular analysis is not indicated when no 5q31-33 breakpoint is found by conventional cytogenetic analysis, because almost all cases reported to date in which 20 metaphases were available for examination have had a cytogenetically detectable abnormality[5].

Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

Before the introduction of imatinib therapy, the median survival was <2 years. Most patients are now known to have excellent morphologic and molecular response to therapy with a recent study showing a 10-year overall survival of 90%[9]. Furthermore, earlier diagnosis due to recognition of this entity will result in earlier initiation of appropriate therapy, preventing cardiac damage and blast phase. Primary and secondary resistance is uncommon; however, initial response typically occurs within 2 months, and if not seen by 3 months, consideration of another therapy is suggested. Whether or not therapy can be stopped in patients with long term molecular remission is still up for debate, with a recent article citing one patient in remission 4 years after therapy cessation[10].

Links

PDGFRB

References

  1. Golub TR, Barker GF, Lovett M, Gilliland DG. Fusion of PDGF receptor-beta to a novel Ets-like gene, Tel, in chronic myelomonocytic leukemia with t(512) chromosomal translocation. Cell. 1994;77(2):307–16.
  2. Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, Kutok J, Clark J, Galinsky I, et al. 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.
  3. 3.0 3.1 Vega F, Medeiros LJ, Bueso-Ramos CE, Arboleda P, Miranda RN. Hematolymphoid neoplasms associated with rearrangements of PDGFRA, PDGFRB, and FGFR1. Am J Clin Pathol. 2015;144(3):377–92.
  4. 4.0 4.1 Steer, E. J., & Cross, N. C. (2002). Myeloproliferative disorders with translocations of chromosome 5q31–35: role of the platelet-derived growth factor receptor Beta. Acta haematologica, 107(2), 113-122.
  5. 5.0 5.1 Swerdlow SH, Campo E, Harris NL, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. In: Bosman FT, Jaffe ES, Lakhani SR, Ohgaki H, eds. World Health Organization Classification of Tumours. Lyon, France: IARC; 2008
  6. Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, Kutok J, Clark J, Galinsky I, et al. 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.
  7. Chen J, Williams IR, Kutok JL, Duclos N, Anastasiadou E, Masters SC, et al. Positive and negative regulatory roles of the WW-like domain in TEL-PDGFbetaR transformation. Blood. 2004;104(2):535–42.
  8. Chang, C. C., & Ohgami, R. S. (Eds.). (2018). Precision molecular pathology of myeloid neoplasms. Springer.
  9. Cheah CY, Burbury K, Apperley JF, Huguet F, Pitini V, Gardembas M, et al. Patients with myeloid malignancies bearing PDGFRB fusion genes achieve durable long-term remissions with imatinib. Blood. 2014;123(23):3574–7.
  10. Cerrano M, Crisà E, Gottardi E, Aguzzi C, Boccadoro M, Ferrero D. Long-term therapy-free remission in a patient with platelet-derived growth factor receptor beta (PDGFRB)- rearranged myeloproliferative neoplasm. Am J Hematol. 2016;91(9):E353.