Compendium of Cancer Genome Aberrations

HAEM5:Myeloid/lymphoid neoplasm with PDGFRA rearrangement: Difference between revisions

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<blockquote class='blockedit'>{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Myeloid/Lymphoid Neoplasms with PDGFRA Rearrangement]].
<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Myeloid/Lymphoid Neoplasms with PDGFRA Rearrangement]].
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Jay Alden, DO
Jay Alden, DO
__TOC__
==WHO Classification of Disease==
==WHO Classification of Disease==


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==Definition / Description of Disease==
==Related Terminology==


Myeloproliferative neoplasms associated with PDGFRA rearrangements are primary/neoplastic hypereosinophilic syndromes associated with recurrent rearrangements of the PDGFRA gene <ref name=":0">Bain BJ, et al., (2017). Myeloid/lymphoid neoplasms with PDGFRA 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, p73-75.</ref>. It is most commonly associated with FIP1L1-PDGFRA (F/P) fusion resulting from a cryptic deletion at 4q12, <ref name=":5">{{Cite journal|last=Cools|first=Jan|last2=DeAngelo|first2=Daniel J.|last3=Gotlib|first3=Jason|last4=Stover|first4=Elizabeth H.|last5=Legare|first5=Robert D.|last6=Cortes|first6=Jorges|last7=Kutok|first7=Jeffrey|last8=Clark|first8=Jennifer|last9=Galinsky|first9=Ilene|date=2003|title=A Tyrosine Kinase Created by Fusion of the PDGFRA and FIP1L1 Genes as a Therapeutic Target of Imatinib in Idiopathic Hypereosinophilic Syndrome|url=http://www.nejm.org/doi/abs/10.1056/NEJMoa025217|journal=New England Journal of Medicine|language=en|volume=348|issue=13|pages=1201–1214|doi=10.1056/NEJMoa025217|issn=0028-4793}}</ref> and often presents as chronic eosinophilic leukemia (CEL), or less commonly, acute myeloid leukemia or T-lymphoblastic leukemia/lymphoma. <ref name=":1">{{Cite journal|last=Metzgeroth|first=G.|last2=Walz|first2=C.|last3=Score|first3=J.|last4=Siebert|first4=R.|last5=Schnittger|first5=S.|last6=Haferlach|first6=C.|last7=Popp|first7=H.|last8=Haferlach|first8=T.|last9=Erben|first9=P.|date=2007|title=Recurrent finding of the FIP1L1-PDGFRA fusion gene in eosinophilia-associated acute myeloid leukemia and lymphoblastic T-cell lymphoma|url=https://www.ncbi.nlm.nih.gov/pubmed/17377585|journal=Leukemia|volume=21|issue=6|pages=1183–1188|doi=10.1038/sj.leu.2404662|issn=0887-6924|pmid=17377585}}</ref>
==Synonyms / Terminology==
Chronic eosinophilic leukemia with FIP1L1-PDGFRA
''FIP1L1-PDGFRA'' –associated chronic eosinophilic leukemia
Myeloid and lymphoid neoplasms associated with PDGFRA rearrangement
PDGFRA-associated Hypereosinophilic syndrome
Myeloid and lymphoid neoplasms with PDGFRA rearrangement
Myeloproliferative variant of the hypereosinophilic syndrome <ref name=":2">{{Cite journal|last=Klion|first=Amy D.|last2=Robyn|first2=Jamie|last3=Akin|first3=Cem|last4=Noel|first4=Pierre|last5=Brown|first5=Margaret|last6=Law|first6=Melissa|last7=Metcalfe|first7=Dean D.|last8=Dunbar|first8=Cynthia|last9=Nutman|first9=Thomas B.|date=2004|title=Molecular remission and reversal of myelofibrosis in response to imatinib mesylate treatment in patients with the myeloproliferative variant of hypereosinophilic syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/14504092|journal=Blood|volume=103|issue=2|pages=473–478|doi=10.1182/blood-2003-08-2798|issn=0006-4971|pmid=14504092}}</ref>
==Epidemiology / Prevalence==
The incidence and prevalence of myeloid/lymphoid neoplasms with PDGFRA rearrangement is not well characterized as demographic data is scarce <ref name=":6">{{Cite journal|last=Shomali|first=William|last2=Gotlib|first2=Jason|date=2019|title=World Health Organization-defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management|url=https://www.ncbi.nlm.nih.gov/pubmed/31423623|journal=American Journal of Hematology|volume=94|issue=10|pages=1149–1167|doi=10.1002/ajh.25617|issn=1096-8652|pmid=31423623}}</ref>. The incidence of HES of any cause is estimated at 0.036 per 100,000, <ref>{{Cite journal|last=Crane|first=Martin M.|last2=Chang|first2=Cindy Ma|last3=Kobayashi|first3=Monica G.|last4=Weller|first4=Peter F.|date=2010|title=Incidence of myeloproliferative hypereosinophilic syndrome in the United States and an estimate of all hypereosinophilic syndrome incidence|url=https://www.ncbi.nlm.nih.gov/pubmed/20639012|journal=The Journal of Allergy and Clinical Immunology|volume=126|issue=1|pages=179–181|doi=10.1016/j.jaci.2010.03.035|issn=1097-6825|pmc=5781228|pmid=20639012}}</ref> though cases in which a causative genetic abnormality constitute a minority of these cases <ref name=":6" />. The F/P rearrangement  is the most common abnormality identified, and is estimated to comprise approximately 10%  of patients with significant hypereosinophilia <ref>{{Cite journal|last=Pardanani|first=Animesh|last2=Brockman|first2=Stephanie R.|last3=Paternoster|first3=Sarah F.|last4=Flynn|first4=Heather C.|last5=Ketterling|first5=Rhett P.|last6=Lasho|first6=Terra L.|last7=Ho|first7=Ching-Liang|last8=Li|first8=Chin-Yang|last9=Dewald|first9=Gordon W.|date=2004|title=FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia|url=https://www.ncbi.nlm.nih.gov/pubmed/15284118|journal=Blood|volume=104|issue=10|pages=3038–3045|doi=10.1182/blood-2004-03-0787|issn=0006-4971|pmid=15284118}}</ref> <ref>{{Cite journal|last=Pardanani|first=A.|last2=Ketterling|first2=R. P.|last3=Li|first3=C.-Y.|last4=Patnaik|first4=M. M.|last5=Wolanskyj|first5=A. P.|last6=Elliott|first6=M. A.|last7=Camoriano|first7=J. K.|last8=Butterfield|first8=J. H.|last9=Dewald|first9=G. W.|date=2006|title=FIP1L1-PDGFRA in eosinophilic disorders: prevalence in routine clinical practice, long-term experience with imatinib therapy, and a critical review of the literature|url=https://www.ncbi.nlm.nih.gov/pubmed/16406016|journal=Leukemia Research|volume=30|issue=8|pages=965–970|doi=10.1016/j.leukres.2005.11.011|issn=0145-2126|pmid=16406016}}</ref>. The entity is recently described, and disorders once called idiopathic hypereosinophilic syndrome are now being classified with genetic testing as specific primary neoplasms  or reactive conditions. The  F/P rearrangment is significantly more common in males with a male:female ratio of about 17:1. The age range varies from ages 7-77 with most patients being between 25 and 55 years. <ref>{{Cite journal|last=Bain|first=Barbara J.|last2=Fletcher|first2=Sarah H.|date=2007|title=Chronic eosinophilic leukemias and the myeloproliferative variant of the hypereosinophilic syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/17868855|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|pmid=17868855}}</ref>
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
{| class="wikitable"
|'''Signs and Symptoms'''
|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
<span class="blue-text">EXAMPLE:</span> Fatigue
<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
|-
|'''Laboratory Findings'''
|<span class="blue-text">EXAMPLE:</span> Cytopenias
<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}</blockquote>
Clinical presentation ranges from asymptomatic to fulminant, life threatening multi-system organ failure. Presenting signs and symptoms are typically related to eosinophilic infiltration, and consistent with hypereosinophilic syndromes of any cause. The largest clinical analysis of patients with hypereosinophilic syndromes (HES) demonstrated the following manifestations at presentation:<ref>{{Cite journal|last=Ogbogu|first=Princess U.|last2=Bochner|first2=Bruce S.|last3=Butterfield|first3=Joseph H.|last4=Gleich|first4=Gerald J.|last5=Huss-Marp|first5=Johannes|last6=Kahn|first6=Jean Emmanuel|last7=Leiferman|first7=Kristin M.|last8=Nutman|first8=Thomas B.|last9=Pfab|first9=Florian|date=2009|title=Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy|url=https://www.ncbi.nlm.nih.gov/pubmed/19910029|journal=The Journal of Allergy and Clinical Immunology|volume=124|issue=6|pages=1319–1325.e3|doi=10.1016/j.jaci.2009.09.022|issn=1097-6825|pmc=2829669|pmid=19910029}}</ref>
*Dermatologic (eg, rash) – 57 percent
*Pulmonary (cough and breathlessness) – 25 percent
*Gastrointestinal – 14 percent
*Cardiac – <5 percent
*Asymptomatic -- 6 percent
Neoplastic PDGFRA-associated hypereosinophilic syndromes are more likely to present with eosinophilic cardiopulmonary disease than HES of any cause. A survey of 44 cases demonstrated skin, spleen, lung, and heart involvement in 57, 52, 45, and 34 percent of cases respectively with a similar rate of asymptomatic cases. <ref name=":8">{{Cite journal|last=Legrand|first=Fanny|last2=Renneville|first2=Aline|last3=MacIntyre|first3=Elizabeth|last4=Mastrilli|first4=Samuel|last5=Ackermann|first5=Felix|last6=Cayuela|first6=Jean Michel|last7=Rousselot|first7=Philippe|last8=Schmidt-Tanguy|first8=Aline|last9=Fain|first9=Olivier|date=2013|title=The Spectrum of FIP1L1-PDGFRA-Associated Chronic Eosinophilic Leukemia: New Insights Based on a Survey of 44 Cases|url=https://www.ncbi.nlm.nih.gov/pubmed/23982058|journal=Medicine|volume=92|issue=5|pages=e1–e9|doi=10.1097/MD.0b013e3182a71eba|issn=1536-5964|pmc=4553979|pmid=23982058}}</ref>
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
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==Sites of Involvement==
Leukemia associated with F/P is a systemic disease occupying the bone marrow and peripheral blood. Neoplastic cells may infiltrate various tissues such as the heart, lungs, nervous systems, skin and GI tract resulting in degranulation and cytokine mediated injury. <ref name=":0" />
==Morphologic Features==
[[File:1-2.jpg|thumb|Hematoxylin and Eosin stained endomyocardial biopsy showing eosinophilic infiltration of endocardium in eosinophilic myocarditis]]
Histopathologic features are dependent on the organs involved. Eosinophilic infiltration is noted on diagnostic tissue biopsy. Eosinophilia and increased eosinophilic precursors can be identified on trephine bone marrow biopsy and peripheral blood smears. There is no histologic correlate to clonality, and genetic studies are required for diagnosis.
[[File:1-14.jpg|thumb|Hematoxylin and Eosin stained section of bone marrow showing increased eosinophils and eosinophilic precursors]]
==Immunophenotype==
These neoplastic eosinophils may express markers of activation such as CD23, CD25, and CD69<ref name=":2" />. The basophils can sometimes be distinguished from those in systemic mastocytosis as CD2 is typically negative in the mast cells of PDGFRA rearrangement, but positive in systemic mastocytosis. <ref name=":3">{{Cite journal|last=Klion|first=Amy D.|last2=Noel|first2=Pierre|last3=Akin|first3=Cem|last4=Law|first4=Melissa A.|last5=Gilliland|first5=D. Gary|last6=Cools|first6=Jan|last7=Metcalfe|first7=Dean D.|last8=Nutman|first8=Thomas B.|date=2003|title=Elevated serum tryptase levels identify a subset of patients with a myeloproliferative variant of idiopathic hypereosinophilic syndrome associated with tissue fibrosis, poor prognosis, and imatinib responsiveness|url=https://www.ncbi.nlm.nih.gov/pubmed/12676775|journal=Blood|volume=101|issue=12|pages=4660–4666|doi=10.1182/blood-2003-01-0006|issn=0006-4971|pmid=12676775}}</ref><ref name=":1" />
{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (subset)||CD25 <ref name=":2" />
|-
|Positive (subset)
|CD23 <ref name=":2" />
|-
|Positive (subset)||CD69 <ref name=":2" />
|-
|Negative (Mast cells)||CD2 <ref name=":3" /><ref name=":1" />
|-
|Posivite (Mast cells, subset
|CD25 <ref name=":3" /><ref name=":1" />
|}
==WHO Essential and Desirable Genetic Diagnostic Criteria==
<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>
{| class="wikitable"
|+
|WHO Essential Criteria (Genetics)*
|
|-
|WHO Desirable Criteria (Genetics)*
|
|-
|Other Classification
|
|}
<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
==Related Terminology==
<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>
{| class="wikitable"
{| class="wikitable"
|+
|+
|Acceptable
|Acceptable
|
|N/A
|-
|-
|Not Recommended
|Not Recommended
|
|Hypereosinophilic syndrome; chronic eosinophilic leukaemia
|}
|}


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<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>
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<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
<blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
* Chromosomal Rearrangements (Gene Fusions)
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Individual Region Genomic Gain/Loss/LOH
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* Gene Mutations (SNV/INDEL)}}</blockquote>
* Gene Mutations (SNV/INDEL)}}</blockquote>


The responsiveness of F/P associated myeloid/lymphoid neoplasms to imatinib mesylate is well documented <ref name=":6" />.  Adverse outcomes are typically related to late presentation, where irreversible organ damage precedes diagnosis, or when the disease is diagnosed in an accelerated phase when complications are more likely. Induction dosing of imatinib ranges from 100-400 mg daily, with much lower maintenence dosing recommended to prevent relapse <ref>{{Cite journal|last=Baccarani|first=Michele|last2=Cilloni|first2=Daniela|last3=Rondoni|first3=Michela|last4=Ottaviani|first4=Emanuela|last5=Messa|first5=Francesca|last6=Merante|first6=Serena|last7=Tiribelli|first7=Mario|last8=Buccisano|first8=Francesco|last9=Testoni|first9=Nicoletta|date=2007|title=The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome. Results of a multicenter prospective study|url=https://www.ncbi.nlm.nih.gov/pubmed/17666373|journal=Haematologica|volume=92|issue=9|pages=1173–1179|doi=10.3324/haematol.11420|issn=1592-8721|pmid=17666373}}</ref> <ref>{{Cite journal|last=Jovanovic|first=Jelena V.|last2=Score|first2=Joannah|last3=Waghorn|first3=Katherine|last4=Cilloni|first4=Daniela|last5=Gottardi|first5=Enrico|last6=Metzgeroth|first6=Georgia|last7=Erben|first7=Philipp|last8=Popp|first8=Helena|last9=Walz|first9=Christoph|date=2007|title=Low-dose imatinib mesylate leads to rapid induction of major molecular responses and achievement of complete molecular remission in FIP1L1-PDGFRA-positive chronic eosinophilic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/17299092|journal=Blood|volume=109|issue=11|pages=4635–4640|doi=10.1182/blood-2006-10-050054|issn=0006-4971|pmid=17299092}}</ref>. Complete hematologic and molecular remission is observed in nearly all patients taking imatinib, usually within 3 months. <ref>{{Cite journal|last=Baccarani|first=Michele|last2=Cilloni|first2=Daniela|last3=Rondoni|first3=Michela|last4=Ottaviani|first4=Emanuela|last5=Messa|first5=Francesca|last6=Merante|first6=Serena|last7=Tiribelli|first7=Mario|last8=Buccisano|first8=Francesco|last9=Testoni|first9=Nicoletta|date=2007|title=The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome. Results of a multicenter prospective study|url=https://www.ncbi.nlm.nih.gov/pubmed/17666373|journal=Haematologica|volume=92|issue=9|pages=1173–1179|doi=10.3324/haematol.11420|issn=1592-8721|pmid=17666373}}</ref> <ref>{{Cite journal|last=Quéméneur|first=Thomas|last2=Mouthon|first2=Luc|last3=Cacoub|first3=Patrice|last4=Meyer|first4=Olivier|last5=Michon-Pasturel|first5=Ulrique|last6=Vanhille|first6=Philippe|last7=Hatron|first7=Pierre-Yves|last8=Guillevin|first8=Loïc|last9=Hachulla|first9=Eric|date=2013|title=Systemic vasculitis during the course of systemic sclerosis: report of 12 cases and review of the literature|url=https://www.ncbi.nlm.nih.gov/pubmed/23263715|journal=Medicine|volume=92|issue=1|pages=1–9|doi=10.1097/MD.0b013e31827781fd|issn=1536-5964|pmc=5370746|pmid=23263715}}</ref> <ref>{{Cite journal|last=Helbig|first=Grzegorz|last2=Stella-Hołowiecka|first2=Beata|last3=Majewski|first3=Mirosław|last4=Całbecka|first4=Małgorzata|last5=Gajkowska|first5=Jolanta|last6=Klimkiewicz|first6=Ryszard|last7=Moskwa|first7=Andrzej|last8=Grzegorczyk|first8=Janina|last9=Lewandowska|first9=Monika|date=2008|title=A single weekly dose of imatinib is sufficient to induce and maintain remission of chronic eosinophilic leukaemia in FIP1L1-PDGFRA-expressing patients|url=https://www.ncbi.nlm.nih.gov/pubmed/18307562|journal=British Journal of Haematology|volume=141|issue=2|pages=200–204|doi=10.1111/j.1365-2141.2008.07033.x|issn=1365-2141|pmid=18307562}}</ref> Imatinib maintains efficacy in accelerated or blast phase disease, and resistance is rare <ref name=":8" /> <ref>{{Cite journal|last=Lierman|first=E.|last2=Michaux|first2=L.|last3=Beullens|first3=E.|last4=Pierre|first4=P.|last5=Marynen|first5=P.|last6=Cools|first6=J.|last7=Vandenberghe|first7=P.|date=2009|title=FIP1L1-PDGFRalpha D842V, a novel panresistant mutant, emerging after treatment of FIP1L1-PDGFRalpha T674I eosinophilic leukemia with single agent sorafenib|url=https://www.ncbi.nlm.nih.gov/pubmed/19212337|journal=Leukemia|volume=23|issue=5|pages=845–851|doi=10.1038/leu.2009.2|issn=1476-5551|pmid=19212337}}</ref>.
The responsiveness of F/P associated myeloid/lymphoid neoplasms to imatinib mesylate is well documented <ref name=":6">{{Cite journal|last=Shomali|first=William|last2=Gotlib|first2=Jason|date=2019|title=World Health Organization-defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management|url=https://www.ncbi.nlm.nih.gov/pubmed/31423623|journal=American Journal of Hematology|volume=94|issue=10|pages=1149–1167|doi=10.1002/ajh.25617|issn=1096-8652|pmid=31423623}}</ref>.  Adverse outcomes are typically related to late presentation, where irreversible organ damage precedes diagnosis, or when the disease is diagnosed in an accelerated phase when complications are more likely. Induction dosing of imatinib ranges from 100-400 mg daily, with much lower maintenence dosing recommended to prevent relapse <ref>{{Cite journal|last=Baccarani|first=Michele|last2=Cilloni|first2=Daniela|last3=Rondoni|first3=Michela|last4=Ottaviani|first4=Emanuela|last5=Messa|first5=Francesca|last6=Merante|first6=Serena|last7=Tiribelli|first7=Mario|last8=Buccisano|first8=Francesco|last9=Testoni|first9=Nicoletta|date=2007|title=The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome. Results of a multicenter prospective study|url=https://www.ncbi.nlm.nih.gov/pubmed/17666373|journal=Haematologica|volume=92|issue=9|pages=1173–1179|doi=10.3324/haematol.11420|issn=1592-8721|pmid=17666373}}</ref> <ref>{{Cite journal|last=Jovanovic|first=Jelena V.|last2=Score|first2=Joannah|last3=Waghorn|first3=Katherine|last4=Cilloni|first4=Daniela|last5=Gottardi|first5=Enrico|last6=Metzgeroth|first6=Georgia|last7=Erben|first7=Philipp|last8=Popp|first8=Helena|last9=Walz|first9=Christoph|date=2007|title=Low-dose imatinib mesylate leads to rapid induction of major molecular responses and achievement of complete molecular remission in FIP1L1-PDGFRA-positive chronic eosinophilic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/17299092|journal=Blood|volume=109|issue=11|pages=4635–4640|doi=10.1182/blood-2006-10-050054|issn=0006-4971|pmid=17299092}}</ref>. Complete hematologic and molecular remission is observed in nearly all patients taking imatinib, usually within 3 months. <ref>{{Cite journal|last=Baccarani|first=Michele|last2=Cilloni|first2=Daniela|last3=Rondoni|first3=Michela|last4=Ottaviani|first4=Emanuela|last5=Messa|first5=Francesca|last6=Merante|first6=Serena|last7=Tiribelli|first7=Mario|last8=Buccisano|first8=Francesco|last9=Testoni|first9=Nicoletta|date=2007|title=The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome. Results of a multicenter prospective study|url=https://www.ncbi.nlm.nih.gov/pubmed/17666373|journal=Haematologica|volume=92|issue=9|pages=1173–1179|doi=10.3324/haematol.11420|issn=1592-8721|pmid=17666373}}</ref> <ref>{{Cite journal|last=Quéméneur|first=Thomas|last2=Mouthon|first2=Luc|last3=Cacoub|first3=Patrice|last4=Meyer|first4=Olivier|last5=Michon-Pasturel|first5=Ulrique|last6=Vanhille|first6=Philippe|last7=Hatron|first7=Pierre-Yves|last8=Guillevin|first8=Loïc|last9=Hachulla|first9=Eric|date=2013|title=Systemic vasculitis during the course of systemic sclerosis: report of 12 cases and review of the literature|url=https://www.ncbi.nlm.nih.gov/pubmed/23263715|journal=Medicine|volume=92|issue=1|pages=1–9|doi=10.1097/MD.0b013e31827781fd|issn=1536-5964|pmc=5370746|pmid=23263715}}</ref> <ref>{{Cite journal|last=Helbig|first=Grzegorz|last2=Stella-Hołowiecka|first2=Beata|last3=Majewski|first3=Mirosław|last4=Całbecka|first4=Małgorzata|last5=Gajkowska|first5=Jolanta|last6=Klimkiewicz|first6=Ryszard|last7=Moskwa|first7=Andrzej|last8=Grzegorczyk|first8=Janina|last9=Lewandowska|first9=Monika|date=2008|title=A single weekly dose of imatinib is sufficient to induce and maintain remission of chronic eosinophilic leukaemia in FIP1L1-PDGFRA-expressing patients|url=https://www.ncbi.nlm.nih.gov/pubmed/18307562|journal=British Journal of Haematology|volume=141|issue=2|pages=200–204|doi=10.1111/j.1365-2141.2008.07033.x|issn=1365-2141|pmid=18307562}}</ref> Imatinib maintains efficacy in accelerated or blast phase disease, and resistance is rare <ref name=":8">{{Cite journal|last=Legrand|first=Fanny|last2=Renneville|first2=Aline|last3=MacIntyre|first3=Elizabeth|last4=Mastrilli|first4=Samuel|last5=Ackermann|first5=Felix|last6=Cayuela|first6=Jean Michel|last7=Rousselot|first7=Philippe|last8=Schmidt-Tanguy|first8=Aline|last9=Fain|first9=Olivier|date=2013|title=The Spectrum of FIP1L1-PDGFRA-Associated Chronic Eosinophilic Leukemia: New Insights Based on a Survey of 44 Cases|url=https://www.ncbi.nlm.nih.gov/pubmed/23982058|journal=Medicine|volume=92|issue=5|pages=e1–e9|doi=10.1097/MD.0b013e3182a71eba|issn=1536-5964|pmc=4553979|pmid=23982058}}</ref> <ref>{{Cite journal|last=Lierman|first=E.|last2=Michaux|first2=L.|last3=Beullens|first3=E.|last4=Pierre|first4=P.|last5=Marynen|first5=P.|last6=Cools|first6=J.|last7=Vandenberghe|first7=P.|date=2009|title=FIP1L1-PDGFRalpha D842V, a novel panresistant mutant, emerging after treatment of FIP1L1-PDGFRalpha T674I eosinophilic leukemia with single agent sorafenib|url=https://www.ncbi.nlm.nih.gov/pubmed/19212337|journal=Leukemia|volume=23|issue=5|pages=845–851|doi=10.1038/leu.2009.2|issn=1476-5551|pmid=19212337}}</ref>.


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{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chr #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)'''
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!'''Clinical Relevance Details/Other Notes'''
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
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!Chromosomal Pattern
!Chromosomal Pattern
!Molecular Pathogenesis
!Molecular Pathogenesis
!'''Prevalence -'''
!Prevalence -  
'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!'''Clinical Relevance Details/Other Notes'''
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
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|}
|}


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<blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}</blockquote>


Cytogenetic studies are usually normal though trisomy of chromosome 8 has been described, and may represent disease evolution <ref name=":0" />.
Cytogenetic studies are usually normal though trisomy of chromosome 8 has been described, and may represent disease evolution <ref name=":0">Bain BJ, et al., (2017). Myeloid/lymphoid neoplasms with PDGFRA 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, p73-75.</ref>.


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{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene!!'''Genetic Alteration'''!!'''Tumor Suppressor Gene, Oncogene, Other'''!!'''Prevalence -'''
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  '''
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!'''Clinical Relevance Details/Other Notes'''
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>''EGFR''
|<span class="blue-text">EXAMPLE:</span>''EGFR''
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|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.


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An activating point mutation in PDGFRA has also been described <ref>{{Cite journal|last=Elling|first=Christian|last2=Erben|first2=Philipp|last3=Walz|first3=Christoph|last4=Frickenhaus|first4=Marie|last5=Schemionek|first5=Mirle|last6=Stehling|first6=Martin|last7=Serve|first7=Hubert|last8=Cross|first8=Nicholas C. P.|last9=Hochhaus|first9=Andreas|date=2011|title=Novel imatinib-sensitive PDGFRA-activating point mutations in hypereosinophilic syndrome induce growth factor independence and leukemia-like disease|url=https://www.ncbi.nlm.nih.gov/pubmed/21224473|journal=Blood|volume=117|issue=10|pages=2935–2943|doi=10.1182/blood-2010-05-286757|issn=1528-0020|pmid=21224473}}</ref>.
An activating point mutation in PDGFRA has also been described <ref>{{Cite journal|last=Elling|first=Christian|last2=Erben|first2=Philipp|last3=Walz|first3=Christoph|last4=Frickenhaus|first4=Marie|last5=Schemionek|first5=Mirle|last6=Stehling|first6=Martin|last7=Serve|first7=Hubert|last8=Cross|first8=Nicholas C. P.|last9=Hochhaus|first9=Andreas|date=2011|title=Novel imatinib-sensitive PDGFRA-activating point mutations in hypereosinophilic syndrome induce growth factor independence and leukemia-like disease|url=https://www.ncbi.nlm.nih.gov/pubmed/21224473|journal=Blood|volume=117|issue=10|pages=2935–2943|doi=10.1182/blood-2010-05-286757|issn=1528-0020|pmid=21224473}}</ref>.
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the F/P tyrosine kinase is thought to become constitutively active in the setting of PDGRA juxtamembrane interruption as breakpoints in the PDGRA gene are tightly clustered, resulting in the removal of a portion of the juxtamembrane domain and activation of the kinase domain upon rearrangement. The role of the FIP1L1 in the neoplastic process is thought to be less significant. <ref>{{Cite journal|last=J. Cools|last2=Gotlib|first2=J.|date=2008|title=Five years since the discovery of FIP1L1–PDGFRA : what we have learned about the fusion and other molecularly defined eosinophilias|url=https://www.nature.com/articles/leu2008287|journal=Leukemia|language=en|volume=22|issue=11|pages=1999–2010|doi=10.1038/leu.2008.287|issn=1476-5551}}</ref>  The eosinophilic proliferation observed in these patients is thought to result from multiple signalling pathways including phosphoinositol 3-kinase, ERK 1/2 and STAT5, though the precise mechanism remains elusive. <ref name=":5" /><ref>{{Cite journal|last=Buitenhuis|first=Miranda|last2=Verhagen|first2=Liesbeth P.|last3=Cools|first3=Jan|last4=Coffer|first4=Paul J.|date=2007|title=Molecular mechanisms underlying FIP1L1-PDGFRA-mediated myeloproliferation|url=https://www.ncbi.nlm.nih.gov/pubmed/17440089|journal=Cancer Research|volume=67|issue=8|pages=3759–3766|doi=10.1158/0008-5472.CAN-06-4183|issn=0008-5472|pmid=17440089}}</ref>
the F/P tyrosine kinase is thought to become constitutively active in the setting of PDGRA juxtamembrane interruption as breakpoints in the PDGRA gene are tightly clustered, resulting in the removal of a portion of the juxtamembrane domain and activation of the kinase domain upon rearrangement. The role of the FIP1L1 in the neoplastic process is thought to be less significant. <ref>{{Cite journal|last=J. Cools|last2=Gotlib|first2=J.|date=2008|title=Five years since the discovery of FIP1L1–PDGFRA : what we have learned about the fusion and other molecularly defined eosinophilias|url=https://www.nature.com/articles/leu2008287|journal=Leukemia|language=en|volume=22|issue=11|pages=1999–2010|doi=10.1038/leu.2008.287|issn=1476-5551}}</ref>  The eosinophilic proliferation observed in these patients is thought to result from multiple signalling pathways including phosphoinositol 3-kinase, ERK 1/2 and STAT5, though the precise mechanism remains elusive. <ref name=":5">{{Cite journal|last=Cools|first=Jan|last2=DeAngelo|first2=Daniel J.|last3=Gotlib|first3=Jason|last4=Stover|first4=Elizabeth H.|last5=Legare|first5=Robert D.|last6=Cortes|first6=Jorges|last7=Kutok|first7=Jeffrey|last8=Clark|first8=Jennifer|last9=Galinsky|first9=Ilene|date=2003|title=A Tyrosine Kinase Created by Fusion of the PDGFRA and FIP1L1 Genes as a Therapeutic Target of Imatinib in Idiopathic Hypereosinophilic Syndrome|url=http://www.nejm.org/doi/abs/10.1056/NEJMoa025217|journal=New England Journal of Medicine|language=en|volume=348|issue=13|pages=1201–1214|doi=10.1056/NEJMoa025217|issn=0028-4793}}</ref><ref>{{Cite journal|last=Buitenhuis|first=Miranda|last2=Verhagen|first2=Liesbeth P.|last3=Cools|first3=Jan|last4=Coffer|first4=Paul J.|date=2007|title=Molecular mechanisms underlying FIP1L1-PDGFRA-mediated myeloproliferation|url=https://www.ncbi.nlm.nih.gov/pubmed/17440089|journal=Cancer Research|volume=67|issue=8|pages=3759–3766|doi=10.1158/0008-5472.CAN-06-4183|issn=0008-5472|pmid=17440089}}</ref>


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(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references />
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references />


'''
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==Notes==
==Notes==
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<nowiki>*</nowiki>''Citation of this Page'': “Myeloid/lymphoid neoplasm with PDGFRA rearrangement”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Myeloid/lymphoid_neoplasm_with_PDGFRA_rearrangement</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “Myeloid/lymphoid neoplasm with PDGFRA rearrangement”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Myeloid/lymphoid_neoplasm_with_PDGFRA_rearrangement</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases M]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:Diseases M]]
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