HAEM5:Myeloid/lymphoid neoplasm with PDGFRB rearrangement - Revision history

Bailey.Glen at 17:24, 3 July 2025

2025-07-03T17:24:33Z

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	~~==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==		==Related Terminology==

Bailey.Glen at 21:44, 25 May 2025

2025-05-25T21:44:45Z

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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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	{\| 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''

Bailey.Glen at 20:20, 25 May 2025

2025-05-25T20:20:19Z

← Older revision		Revision as of 15:20, 25 May 2025
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	<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>].		<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==		==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
	\|		\|Myeloid/lymphoid neoplasms with PDGFRB rearrangement; chronic myelomonocytic leukaemia with eosinophilia associated with t(5;12); myeloid neoplasms associated with PDGFRB rearrangement
	\|-		\|-
	\|Not Recommended		\|Not Recommended
	\|		\|N/A
	\|}		\|}

Bailey.Glen at 17:42, 24 March 2025

2025-03-24T17:42:52Z

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	{{DISPLAYTITLE:Myeloid/lymphoid neoplasm with PDGFRB rearrangement}}		{{DISPLAYTITLE:Myeloid/lymphoid neoplasm with PDGFRB rearrangement}}

	[[HAEM5:Table_of_Contents\|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]		[[HAEM5:Table_of_Contents\|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]

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

	~~__TOC__~~

	==WHO Classification of Disease==		==WHO Classification of Disease==

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2025-02-11T14:16:35Z

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Bailey.Glen at 18:55, 10 February 2025

2025-02-10T18:55:32Z

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Bailey.Glen at 18:27, 10 February 2025

2025-02-10T18:27:27Z

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	<blockquote class='blockedit'>{{Box-round\|title=v4:Clinical Features\|The content below was from the old template. Please incorporate above.}}		<blockquote class='blockedit'>{{Box-round\|title=v4:Clinical Features\|The content below was from the old template. Please incorporate above.}}</blockquote>
	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.		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.

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	==Sites of Involvement==		==Sites of Involvement==
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	<blockquote class='blockedit'>{{Box-round\|title=v4:Immunophenotype\|The content below was from the old template. Please incorporate above.}}		<blockquote class='blockedit'>{{Box-round\|title=v4:Immunophenotype\|The content below was from the old template. Please incorporate above.}}</blockquote>

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

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	==Chromosomal Rearrangements (Gene Fusions)==		==Chromosomal Rearrangements (Gene Fusions)==
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	* Individual Region Genomic Gain/Loss/LOH		* Individual Region Genomic Gain/Loss/LOH
	* Characteristic Chromosomal Patterns		* Characteristic Chromosomal Patterns
	* Gene Mutations (SNV/INDEL)}}		* Gene Mutations (SNV/INDEL)}}</blockquote>

	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>.		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>.

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	==Individual Region Genomic Gain / Loss / LOH==		==Individual Region Genomic Gain / Loss / LOH==
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	t(5:12)(q32;p13.2), translocation resulting in ETV6-PDGFRB.		t(5:12)(q32;p13.2), translocation resulting in ETV6-PDGFRB.
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	==Gene Mutations (SNV / INDEL)==		==Gene Mutations (SNV / INDEL)==
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	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>.		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>.

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	==Epigenomic Alterations==		==Epigenomic Alterations==
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	<blockquote class='blockedit'>{{Box-round\|title=v4:Genes and Main Pathways Involved\|The content below was from the old template. Please incorporate above.}}		<blockquote class='blockedit'>{{Box-round\|title=v4:Genes and Main Pathways Involved\|The content below was from the old template. Please incorporate above.}}</blockquote>
	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>.		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>.

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	==Genetic Diagnostic Testing Methods==		==Genetic Diagnostic Testing Methods==

Bailey.Glen at 22:21, 6 September 2024

2024-09-06T22:21:33Z

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	__TOC__		__TOC__

	==~~Cancer Category / Type~~==		==WHO Classification of Disease==

	Myeloid ~~Neoplasms~~/~~Acute myeloid leukemia~~		{\| class="wikitable"
			!Structure
	~~==Cancer Sub~~-~~Classification /~~ Subtype==		!Disease
			\|-
	Myeloid/~~Lymphoid Neoplasms~~ with PDGFRB ~~Rearrangement~~		\|Book
			\|Haematolymphoid Tumours (5th ed.)
			\|-
			\|Category
			\|Myeloid proliferations and neoplasms
			\|-
			\|Family
			\|Myeloid/lymphoid neoplasms
			\|-
			\|Type
			\|Myeloid/lymphoid neoplasms with eosinophilia and defining gene rearrangement
			\|-
			\|Subtype(s)
			\|Myeloid/lymphoid neoplasm with PDGFRB rearrangement
			\|}

	==Definition / Description of Disease==		==Definition / Description of Disease==

Bailey.Glen at 22:06, 6 September 2024

2024-09-06T22:06:48Z

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Bailey.Glen at 19:34, 13 December 2023

2023-12-13T19:34:18Z

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	<blockquote class='blockedit'>{{Box-round\|title=HAEM5 Conversion Notes\|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Myeloid/Lymphoid Neoplasms with PDGFRB Rearrangement]].		<blockquote class='blockedit'>{{Box-round\|title=HAEM5 Conversion Notes\|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Myeloid/Lymphoid Neoplasms with PDGFRB Rearrangement]].
	}}</blockquote>		}}</blockquote>

			<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples). Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)\|<u>FAQs</u>]] as well as contact your [[Leadership\|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span>

	==Primary Author(s)*==		==Primary Author(s)*==