HAEM5:Myeloid/lymphoid neoplasm with JAK2 rearrangement - Revision history

Bailey.Glen at 17:24, 3 July 2025

2025-07-03T17:24:27Z

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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 21:43, 25 May 2025

2025-05-25T21:43:56Z

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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

2025-05-25T20:20:14Z

← 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 PCM1::JAK2
	\|-		\|-
	\|Not Recommended		\|Not Recommended
	\|		\|N/A
	\|}		\|}

Bailey.Glen at 17:42, 24 March 2025

2025-03-24T17:42:47Z

← Older revision		Revision as of 12:42, 24 March 2025
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	{{DISPLAYTITLE:Myeloid/lymphoid neoplasm with JAK2 rearrangement}}		{{DISPLAYTITLE:Myeloid/lymphoid neoplasm with JAK2 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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	Jessica Snider, M.D. and Daynna J. Wolff, PhD		Jessica Snider, M.D. and Daynna J. Wolff, PhD

	~~__TOC__~~

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

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2025-02-11T14:19:01Z

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Bailey.Glen at 18:55, 10 February 2025

2025-02-10T18:55:26Z

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Bailey.Glen at 18:27, 10 February 2025

2025-02-10T18:27:22Z

← Older revision		Revision as of 13:27, 10 February 2025
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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 features of a myeloproliferative disorder or MDS/MPN and most have eosinophilia and/or bone marrow fibrosis<ref name=":2" /><ref name=":1">{{Cite journal\|last=Hoeller\|first=Sylvia\|last2=Walz\|first2=Christoph\|last3=Reiter\|first3=Andreas\|last4=Dirnhofer\|first4=Stephan\|last5=Tzankov\|first5=Alexandar\|date=2011\|title=PCM1–JAK2-fusion: a potential treatment target in myelodysplastic–myeloproliferative and other hemato-lymphoid neoplasms\|url=http://www.tandfonline.com/doi/full/10.1517/14728222.2011.538683\|journal=Expert Opinion on Therapeutic Targets\|language=en\|volume=15\|issue=1\|pages=53–62\|doi=10.1517/14728222.2011.538683\|issn=1472-8222}}</ref>. Patients in chronic phase tend to progress to AML quickly; some present with de novo acute leukemia, either myeloid or lymphoid<ref name=":1" /><ref name=":2" /><sup> </sup>		Patients typically present with features of a myeloproliferative disorder or MDS/MPN and most have eosinophilia and/or bone marrow fibrosis<ref name=":2" /><ref name=":1">{{Cite journal\|last=Hoeller\|first=Sylvia\|last2=Walz\|first2=Christoph\|last3=Reiter\|first3=Andreas\|last4=Dirnhofer\|first4=Stephan\|last5=Tzankov\|first5=Alexandar\|date=2011\|title=PCM1–JAK2-fusion: a potential treatment target in myelodysplastic–myeloproliferative and other hemato-lymphoid neoplasms\|url=http://www.tandfonline.com/doi/full/10.1517/14728222.2011.538683\|journal=Expert Opinion on Therapeutic Targets\|language=en\|volume=15\|issue=1\|pages=53–62\|doi=10.1517/14728222.2011.538683\|issn=1472-8222}}</ref>. Patients in chronic phase tend to progress to AML quickly; some present with de novo acute leukemia, either myeloid or lymphoid<ref name=":1" /><ref name=":2" /><sup> </sup>
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	In general, patients with this disorder have weakness/fatigue (~26%), cough (~24%), myaligias/angioedema (~14%), rash or fever (~12%) and rhinitis (~10%)<ref>{{Cite journal\|last=Gotlib\|first=Jason\|date=2017\|title=World Health Organization-defined eosinophilic disorders: 2017 update on diagnosis, risk stratification, and management\|url=http://doi.wiley.com/10.1002/ajh.24880\|journal=American Journal of Hematology\|language=en\|volume=92\|issue=11\|pages=1243–1259\|doi=10.1002/ajh.24880}}</ref> ; lymphadenopathy and splenomegaly are common<ref name=":2" />		In general, patients with this disorder have weakness/fatigue (~26%), cough (~24%), myaligias/angioedema (~14%), rash or fever (~12%) and rhinitis (~10%)<ref>{{Cite journal\|last=Gotlib\|first=Jason\|date=2017\|title=World Health Organization-defined eosinophilic disorders: 2017 update on diagnosis, risk stratification, and management\|url=http://doi.wiley.com/10.1002/ajh.24880\|journal=American Journal of Hematology\|language=en\|volume=92\|issue=11\|pages=1243–1259\|doi=10.1002/ajh.24880}}</ref> ; lymphadenopathy and splenomegaly are common<ref name=":2" />

			<blockquote class="blockedit">
			<center><span style="color:Maroon">'''End of V4 Section'''</span>
			----
	</blockquote>		</blockquote>
	==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>

	IHC can be used to characterize acute myeloid transformation and myeloblasts express dim CD45, dim CD34, dim CD117, HLA-DR, dim CD33, and dim CD13<ref name=":0" />. In addition, For the cases with lymphoid components, IHC can assist with assessment and show dim CD19 and dim CD10, consistent with lymphoblast lineage<ref name=":0" /><ref name=":2" />.		IHC can be used to characterize acute myeloid transformation and myeloblasts express dim CD45, dim CD34, dim CD117, HLA-DR, dim CD33, and dim CD13<ref name=":0" />. In addition, For the cases with lymphoid components, IHC can assist with assessment and show dim CD19 and dim CD10, consistent with lymphoblast lineage<ref name=":0" /><ref name=":2" />.

			<blockquote class="blockedit">
			<center><span style="color:Maroon">'''End of V4 Section'''</span>
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	==Chromosomal Rearrangements (Gene Fusions)==		==Chromosomal Rearrangements (Gene Fusions)==
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	{\| class="wikitable sortable"		{\| class="wikitable sortable"
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			<blockquote class="blockedit">
			<center><span style="color:Maroon">'''End of V4 Section'''</span>
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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>
	Most patients present with MPN with variable degrees of eosinophilia in blood and/or bone marrow, frequent marrow fibrosis, and large aggregates of immature erythroid precursors, and clinically exhibit hepatosplenomegagly and lymphadenopathy<ref name=":2" />. However, diagnosis may be difficult in cases without obvious eosinophilia.		Most patients present with MPN with variable degrees of eosinophilia in blood and/or bone marrow, frequent marrow fibrosis, and large aggregates of immature erythroid precursors, and clinically exhibit hepatosplenomegagly and lymphadenopathy<ref name=":2" />. However, diagnosis may be difficult in cases without obvious eosinophilia.

	Due to the variations in presentation, the prognosis is mainly dependent on the phase at presentation, but generally tends to have an aggressive course<sup>1</sup>. There currently are no approved therapies for ''PCM1/JAK2''-mediated myeloid/lymphoid neoplasm with eosinophilia; however, ''JAK2'' inhibitors have been approved for other hematopoietic neoplasms with constitutively activated ''JAK2'' kinases.<sup>2</sup>		Due to the variations in presentation, the prognosis is mainly dependent on the phase at presentation, but generally tends to have an aggressive course<sup>1</sup>. There currently are no approved therapies for ''PCM1/JAK2''-mediated myeloid/lymphoid neoplasm with eosinophilia; however, ''JAK2'' inhibitors have been approved for other hematopoietic neoplasms with constitutively activated ''JAK2'' kinases.<sup>2</sup>

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			<center><span style="color:Maroon">'''End of V4 Section'''</span>
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	==Individual Region Genomic Gain / Loss / LOH==		==Individual Region Genomic Gain / Loss / LOH==
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	There are no known recurrent genomic loss/gain or LOH pattern associated with entity.		There are no known recurrent genomic loss/gain or LOH pattern associated with entity.
			<blockquote class="blockedit">
			<center><span style="color:Maroon">'''End of V4 Section'''</span>
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	==Characteristic Chromosomal Patterns==		==Characteristic Chromosomal Patterns==
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	There are no known secondary chromosomal changes and no pattern of other chromosome aberrations.		There are no known secondary chromosomal changes and no pattern of other chromosome aberrations.

			<blockquote class="blockedit">
			<center><span style="color:Maroon">'''End of V4 Section'''</span>
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	==Gene Mutations (SNV / INDEL)==		==Gene Mutations (SNV / INDEL)==
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	Given the rarity of the entity, there are no known recurrent aberrations. For the largest series studied, most cases were negative for mutations. However, some cases showed variants in genes associated with myeloid malignancies (ASXL1, RUNX1, SRSF2, TET2, BCOR) and one patient with B-ALL transformation showed variants in ETV6 and TP53<ref name=":2" />		Given the rarity of the entity, there are no known recurrent aberrations. For the largest series studied, most cases were negative for mutations. However, some cases showed variants in genes associated with myeloid malignancies (ASXL1, RUNX1, SRSF2, TET2, BCOR) and one patient with B-ALL transformation showed variants in ETV6 and TP53<ref name=":2" />
	===Other Mutations===		===Other Mutations===
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			<center><span style="color:Maroon">'''End of V4 Section'''</span>
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	==Epigenomic Alterations==		==Epigenomic Alterations==
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	''PCM1'' (pericentriolar material 1) is a protein present in cytoplasmic granules and can be found in association with the centrosome. ''PCM1'' is indirectly responsible for microtubule anchoring, which is necessary for a variety of cellular functions, including intracellular transport and cell division. The gene is located at band 8p22 and includes 41 exons.<sup>5</sup>		''PCM1'' (pericentriolar material 1) is a protein present in cytoplasmic granules and can be found in association with the centrosome. ''PCM1'' is indirectly responsible for microtubule anchoring, which is necessary for a variety of cellular functions, including intracellular transport and cell division. The gene is located at band 8p22 and includes 41 exons.<sup>5</sup>
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	The PCM1-JAK2 fusion product retains the coiled-coil domains of ''PCM1'' and the activating tyrosine kinase domain of ''JAK2''. Thus PCM1-JAK2 fusion produces an aberrant tyrosine kinase that results in constitutive activation of the JAK2–STAT pathway<ref name=":1" />		The PCM1-JAK2 fusion product retains the coiled-coil domains of ''PCM1'' and the activating tyrosine kinase domain of ''JAK2''. Thus PCM1-JAK2 fusion produces an aberrant tyrosine kinase that results in constitutive activation of the JAK2–STAT pathway<ref name=":1" />

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			<center><span style="color:Maroon">'''End of V4 Section'''</span>
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	==Genetic Diagnostic Testing Methods==		==Genetic Diagnostic Testing Methods==

Bailey.Glen at 22:21, 6 September 2024

2024-09-06T22:21:41Z

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	__TOC__		__TOC__

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

	~~Acute~~ Myeloid ~~Leukemia~~/Myeloid/lymphoid ~~neoplasm~~ with eosinophilia		{\| class="wikitable"
			!Structure
	~~==Cancer Sub-Classification /~~ Subtype==		!Disease
			\|-
	~~''PCM1/JAK2''-Mediated myeloid~~/lymphoid neoplasm with ~~eosinophilia~~		\|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 JAK2 rearrangement
			\|}

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

Bailey.Glen at 22:06, 6 September 2024

2024-09-06T22:06:01Z

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Bailey.Glen at 19:34, 13 December 2023

2023-12-13T19:34:14Z

← Older revision		Revision as of 14:34, 13 December 2023
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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 PCM1-JAK2]].		<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 PCM1-JAK2]].
	}}</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)*==