HAEM5:T-large granular lymphocytic leukaemia - Revision history

Nicolas.LaScala: /* Epigenomic Alterations */

2026-01-17T01:10:57Z

Epigenomic Alterations

← Older revision		Revision as of 20:10, 16 January 2026
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	**An epigenetic inhibition mechanism to SOCS3 gene is hypothesized<ref name=":10" />		**An epigenetic inhibition mechanism to SOCS3 gene is hypothesized<ref name=":10" />
	**KIR3DL1 has been shown to be down-modulated by hypermethylation of the promoter<ref name=":10" />		**KIR3DL1 has been shown to be down-modulated by hypermethylation of the promoter<ref name=":10" />
	**Mutations in KMT2D and TET2 have been found to significantly co-occur with STAT3 mutations<~~sup>[26]<~~/~~sup~~>		**Mutations in KMT2D and TET2 have been found to significantly co-occur with STAT3 mutations<ref name=":0" />

	<br />		<br />
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	==Genes and Main Pathways Involved==		==Genes and Main Pathways Involved==

			<span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
	~~Put your text here and fill in the table~~ <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
	{\| class="wikitable sortable"		{\| class="wikitable sortable"
	\|-		\|-
	!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome		!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
	\|-		\|-
	\|JAK/STAT<~~sup>[7]<~~/~~sup~~>		\|JAK/STAT<ref name=":3" />
	\|Constitutive activation		\|Constitutive activation
	\|Dysregulation of apoptosis		\|Dysregulation of apoptosis
	\|-		\|-
	\|NK-kB<~~sup>[7]<~~/~~sup~~>		\|NK-kB<ref name=":3" />
	\|Pathway activation		\|Pathway activation
	\|Preventing apoptosis		\|Preventing apoptosis
	\|-		\|-
	\|FAS and FASL<~~sup>[7]<~~/~~sup~~>		\|FAS and FASL<ref name=":3" />
	\|Resistance to FAS mediated apoptosis		\|Resistance to FAS mediated apoptosis
	\|Activation of pro-survival pathways which is postulated to lead to neutropenia		\|Activation of pro-survival pathways which is postulated to lead to neutropenia
	\|-		\|-
	\|RAS/RAF1/MEK1/ERK<~~sup>[7]<~~/~~sup~~>		\|RAS/RAF1/MEK1/ERK<ref name=":3" />
	\|Overactive RAS		\|Overactive RAS
	\|Constitutive activation of RAS and ERK		\|Constitutive activation of RAS and ERK
	\|-		\|-
	\|PI3K/AKT<~~sup>[7]<~~/~~sup~~>		\|PI3K/AKT<ref name=":3" />
	\|Dysregulation		\|Dysregulation
	\|Apoptosis inhibition		\|Apoptosis inhibition
Line 394:		Line 393:
	*Morphologic assessment, flow cytometry and immunohistochemistry		*Morphologic assessment, flow cytometry and immunohistochemistry
	*PCR to assess for clonality, T-cell receptor (TCR) gene rearrangements		*PCR to assess for clonality, T-cell receptor (TCR) gene rearrangements
	** TCR gamma (TCRG) gene is rearranged in all cases, regardless of the type of TCR expressed, thus proves clonality		** TCR gamma (TCRG) gene is rearranged in all cases, regardless of the type of TCR expressed, thus proves clonality<ref name=":9" />
	** Can be helpful in differentiating a reactive lymphocytosis from clonal T-LGL's		** Can be helpful in differentiating a reactive lymphocytosis from clonal T-LGL's
	*** NK LGL proliferations do not express TCR, making assessment of clonality difficult		*** NK LGL proliferations do not express TCR, making assessment of clonality difficult<ref name=":3" />
	*** Expression of activating isoforms of killer immunoglobulin-like receptors (KIR) can be used as a surrogate marker of clonality in NK LGL		*** Expression of activating isoforms of killer immunoglobulin-like receptors (KIR) can be used as a surrogate marker of clonality in NK LGL<ref name=":3" />
	* Myeloid neoplasms may present with clonal large granular lymphocyte expansion with STAT3/STAT5B mutations. Next generation sequencing can be diagnostically useful in these cases<~~sup~~>~~[21]~~</~~sup~~>		* Myeloid neoplasms may present with clonal large granular lymphocyte expansion with STAT3/STAT5B mutations. Next generation sequencing can be diagnostically useful in these cases<ref>{{Cite journal\|last=Kavesh\|first=Mark\|last2=Mohebnasab\|first2=Maedeh\|last3=Angel\|first3=Marcela Riveros\|last4=Xie\|first4=Wei\|last5=Raess\|first5=Philipp W.\|last6=Cui\|first6=Wei\|last7=Press\|first7=Richard D.\|last8=Yang\|first8=Guang\|last9=Li\|first9=Peng\|date=2023-01-10\|title=Distinguishing STAT3/STAT5B -mutated large granular lymphocyte leukemia from myeloid neoplasms by genetic profiling\|url=https://ashpublications.org/bloodadvances/article/7/1/40/486140/Distinguishing-STAT3-STAT5B-mutated-large-granular\|journal=Blood Advances\|language=en\|volume=7\|issue=1\|pages=40–45\|doi=10.1182/bloodadvances.2022008192\|issn=2473-9529}}</ref>

	==Familial Forms==		==Familial Forms==
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	==Additional Information==		==Additional Information==

	*PI3K-Akt has been found to be upregulated in KLRG1<sup>-</sup> CD8<sup>+</sup> T-LGLL. Studies are being conducted to examine treatment with linperlisib.<~~sup~~>~~[29]~~</~~sup~~>		*PI3K-Akt has been found to be upregulated in KLRG1<sup>-</sup> CD8<sup>+</sup> T-LGLL. Studies are being conducted to examine treatment with linperlisib.<ref>{{Cite journal\|last=Zhang\|first=Lele\|last2=Qiu\|first2=Chen\|last3=Li\|first3=Ruonan\|last4=Shen\|first4=Yucan\|last5=Tian\|first5=Linzhu\|last6=Chang\|first6=Hong\|last7=Liang\|first7=Qian\|last8=Pan\|first8=Hong\|last9=Gao\|first9=Zhen\|date=2025-04\|title=KLRG1 re-defines a leukemic clone of CD8 effector T cells sensitive to PI3K inhibitor in T cell large granular lymphocytic leukemia\|url=https://linkinghub.elsevier.com/retrieve/pii/S2666379125001090\|journal=Cell Reports Medicine\|language=en\|volume=6\|issue=4\|pages=102036\|doi=10.1016/j.xcrm.2025.102036\|pmc=12047471\|pmid=40147444}}</ref>
	*Myleoid clonal hematopoiesis is associated with the presence of cytopenia in LGLL<~~sup>[30]<~~/~~sup~~>		*Myleoid clonal hematopoiesis is associated with the presence of cytopenia in LGLL<ref name=":1" />

	==Links==		==Links==

Nicolas.LaScala: /* Gene Mutations (SNV/INDEL) */

2026-01-17T01:03:48Z

Gene Mutations (SNV/INDEL)

Show changes

Nicolas.LaScala: /* Gene Mutations (SNV/INDEL) */

2026-01-16T21:26:05Z

Gene Mutations (SNV/INDEL)

← Older revision		Revision as of 16:26, 16 January 2026
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	F127C <ref>{{Cite journal\|last=Johansson\|first=Patricia\|last2=Bergmann\|first2=Anke\|last3=Rahmann\|first3=Sven\|last4=Wohlers\|first4=Inken\|last5=Scholtysik\|first5=René\|last6=Przekopowitz\|first6=Martina\|last7=Seifert\|first7=Marc\|last8=Tschurtschenthaler\|first8=Gertraud\|last9=Webersinke\|first9=Gerald\|date=2016-01-01\|title=Recurrent alterations of TNFAIP 3 (A20) in T-cell large granular lymphocytic leukemia: A20 mutations in T-LGL\|url=https://onlinelibrary.wiley.com/doi/10.1002/ijc.29697\|journal=International Journal of Cancer\|language=en\|volume=138\|issue=1\|pages=121–124\|doi=10.1002/ijc.29697}}</ref>		F127C <ref>{{Cite journal\|last=Johansson\|first=Patricia\|last2=Bergmann\|first2=Anke\|last3=Rahmann\|first3=Sven\|last4=Wohlers\|first4=Inken\|last5=Scholtysik\|first5=René\|last6=Przekopowitz\|first6=Martina\|last7=Seifert\|first7=Marc\|last8=Tschurtschenthaler\|first8=Gertraud\|last9=Webersinke\|first9=Gerald\|date=2016-01-01\|title=Recurrent alterations of TNFAIP 3 (A20) in T-cell large granular lymphocytic leukemia: A20 mutations in T-LGL\|url=https://onlinelibrary.wiley.com/doi/10.1002/ijc.29697\|journal=International Journal of Cancer\|language=en\|volume=138\|issue=1\|pages=121–124\|doi=10.1002/ijc.29697}}</ref>
	\|Other <ref>{{Cite journal\|title=TNFAIP3 TNF alpha induced protein 3 [Homo sapiens (human)] - Gene - NCBI\|url=https://www.ncbi.nlm.nih.gov/gene/7128\|language=en}}</ref>		\|Other <ref>{{Cite journal\|title=TNFAIP3 TNF alpha induced protein 3 [Homo sapiens (human)] - Gene - NCBI\|url=https://www.ncbi.nlm.nih.gov/gene/7128\|language=en}}</ref>
	\|Recurrent <~~sup~~>~~[46]~~</~~sup~~>		\|Recurrent <ref name=":16">{{Cite journal\|last=Upadhyayula\|first=Bhanu Surabi\|last2=Saglimbeni\|first2=Grace S.\|last3=Gobel\|first3=Edie\|last4=Gobel\|first4=Abbi\|last5=Morris\|first5=Tyson J.\|last6=Surendra\|first6=Akaash\|last7=Hsia\|first7=Beau\|last8=Sood\|first8=Akshat\|last9=Tauseef\|first9=Abubakar\|date=2026-01\|title=Mutational Spectrum of T-Cell Large Granular Lymphocytic Leukemia: Insights From the AACR Project GENIE Consortium\|url=http://cgp.iiarjournals.org/lookup/doi/10.21873/cgp.20566\|journal=Cancer Genomics - Proteomics\|language=en\|volume=23\|issue=1\|pages=135–143\|doi=10.21873/cgp.20566\|issn=1109-6535\|pmc=12758657\|pmid=41482347}}</ref>
	\|P,T		\|P,T
	\|WHO		\|WHO
	\|TNFAIP 3 mutation has been correlated with increased overall survival <~~sup~~>~~[17]~~</~~sup~~>		\|TNFAIP 3 mutation has been correlated with increased overall survival <ref>{{Cite journal\|last=Chen\|first=Cunte\|last2=Chen\|first2=Zheng\|last3=Huang\|first3=Ling\|last4=Zhou\|first4=Lingling\|last5=Zhu\|first5=Lihua\|last6=Liu\|first6=Sichu\|last7=Luo\|first7=Gengxin\|last8=Li\|first8=Wenyu\|last9=Zeng\|first9=Chengwu\|date=2021-09-15\|title=TNFAIP3 mutation may be associated with favorable overall survival for patients with T-cell lymphoma\|url=https://doi.org/10.1186/s12935-021-02191-5\|journal=Cancer Cell International\|language=en\|volume=21\|issue=1\|pages=490\|doi=10.1186/s12935-021-02191-5\|issn=1475-2867\|pmc=8444556\|pmid=34526012}}</ref>
			TNFAIP3 itself is a NF‐κB target gene<ref>{{Cite journal\|last=Zhang\|first=Ranran\|last2=Shah\|first2=Mithun Vinod\|last3=Yang\|first3=Jun\|last4=Nyland\|first4=Susan B.\|last5=Liu\|first5=Xin\|last6=Yun\|first6=Jong K.\|last7=Albert\|first7=Réka\|last8=Loughran\|first8=Thomas P.\|date=2008-10-21\|title=Network model of survival signaling in large granular lymphocyte leukemia\|url=https://www.pnas.org/doi/full/10.1073/pnas.0806447105\|journal=Proceedings of the National Academy of Sciences\|volume=105\|issue=42\|pages=16308–16313\|doi=10.1073/pnas.0806447105\|pmc=2571012\|pmid=18852469}}</ref>

			In one study three of four of the patients with non‐synonymous TNFAIP3 alterations also harbored a STAT3 mutation (''p'' = 0.004)<ref name=":11" />

	~~TNFAIP3 itself is a NF‐κB target gene<sup>[15]</sup>~~

	In one study three of four of the patients with non‐synonymous TNFAIP3 alterations also harbored a STAT3 mutation (''p'' = 0.004)<~~sup>[9]<~~/~~sup~~>
	\|-		\|-
	\|TET2 <~~sup>[1]<~~/~~sup~~>		\|TET2 <ref name=":9" />
	\|Loss of function <~~sup~~>~~[26]~~</~~sup~~>		\|Loss of function <ref>{{Cite journal\|last=Cheon\|first=HeeJin\|last2=Xing\|first2=Jeffrey C.\|last3=Moosic\|first3=Katharine B.\|last4=Ung\|first4=Johnson\|last5=Chan\|first5=Vivian W.\|last6=Chung\|first6=David S.\|last7=Toro\|first7=Mariella F.\|last8=Elghawy\|first8=Omar\|last9=Wang\|first9=John S.\|date=2022-05-19\|title=Genomic landscape of TCRαβ and TCRγδ T-large granular lymphocyte leukemia\|url=https://ashpublications.org/blood/article/139/20/3058/483429/Genomic-landscape-of-TCR-and-TCR-T-large-granular\|journal=Blood\|language=en\|volume=139\|issue=20\|pages=3058–3072\|doi=10.1182/blood.2021013164\|issn=0006-4971\|pmc=9121841\|pmid=35015834}}</ref>
	\|Other <~~sup~~>[34]</~~sup~~>		\|Other <ref>{{Cite journal\|title=TET2 tet methylcytosine dioxygenase 2 [Homo sapiens (human)] - Gene - NCBI\|url=https://www.ncbi.nlm.nih.gov/gene/54790}}</ref>
	\|Common <~~sup>[46]<~~/~~sup~~>		\|Common <ref name=":16" />
	\|N/A		\|N/A
	\|WHO		\|WHO
	\|Found to be the most prevalent mutation in myeloid neoplasm or myeloid clonal hematopoiesis coexisting with T-LGLL <~~sup~~>~~[30]~~</~~sup~~>		\|Found to be the most prevalent mutation in myeloid neoplasm or myeloid clonal hematopoiesis coexisting with T-LGLL <ref>{{Cite journal\|last=Kawashima\|first=Naomi\|last2=Gurnari\|first2=Carmelo\|last3=Bravo-Perez\|first3=Carlos\|last4=Kubota\|first4=Yasuo\|last5=Pagliuca\|first5=Simona\|last6=Guarnera\|first6=Luca\|last7=Williams\|first7=Nakisha D.\|last8=Durmaz\|first8=Arda\|last9=Ahmed\|first9=Arooj\|date=2025-02\|title=Clonal hematopoiesis in large granular lymphocytic leukemia\|url=https://www.nature.com/articles/s41375-024-02460-y\|journal=Leukemia\|language=en\|volume=39\|issue=2\|pages=451–459\|doi=10.1038/s41375-024-02460-y\|issn=1476-5551}}</ref>
	\|-		\|-
	\|BCL11B <~~sup>[1]<~~/~~sup~~>		\|BCL11B <ref name=":9" />
	\|Missense H126R <~~sup~~>~~[43]~~</~~sup~~>		\|Missense H126R<ref name=":17">{{Cite journal\|last=Andersson\|first=E. I.\|last2=Rajala\|first2=H. L. M.\|last3=Eldfors\|first3=S.\|last4=Ellonen\|first4=P.\|last5=Olson\|first5=T.\|last6=Jerez\|first6=A.\|last7=Clemente\|first7=M. J.\|last8=Kallioniemi\|first8=O.\|last9=Porkka\|first9=K.\|date=2013-12\|title=Novel somatic mutations in large granular lymphocytic leukemia affecting the STAT-pathway and T-cell activation\|url=https://www.nature.com/articles/bcj201365\|journal=Blood Cancer Journal\|language=en\|volume=3\|issue=12\|pages=e168–e168\|doi=10.1038/bcj.2013.65\|issn=2044-5385\|pmc=3877422\|pmid=24317090}}</ref>
	\|Other <~~sup~~>~~[35]~~</~~sup~~>		\|Other<ref>{{Cite journal\|title=BCL11 transcription factor B\|url=https://www.ncbi.nlm.nih.gov/datasets/gene/64919/\|language=en}}</ref>
	\|Rare <~~sup>[43]<~~/~~sup~~>		\|Rare<ref name=":17" />
	\|N/A		\|N/A
	\|WHO		\|WHO
	\|BCL11B is required for T-cell survival and overexpression could effectively increase T-cell activation and proliferation. <~~sup>[43]<~~/~~sup~~>		\|BCL11B is required for T-cell survival and overexpression could effectively increase T-cell activation and proliferation.<ref name=":17" />
	\|-		\|-
	\|FLT3 <~~sup>[1]<~~/~~sup~~>		\|FLT3<ref name=":9" />
	\|A high-impact Asp228Gly variant on JAK STAT has been demonstrated <~~sup~~>~~[44]~~</~~sup~~>		\|A high-impact Asp228Gly variant on JAK STAT has been demonstrated <ref name=":18">{{Cite journal\|last=Coppe\|first=A\|last2=Andersson\|first2=E I\|last3=Binatti\|first3=A\|last4=Gasparini\|first4=V R\|last5=Bortoluzzi\|first5=S\|last6=Clemente\|first6=M\|last7=Herling\|first7=M\|last8=Maciejewski\|first8=J\|last9=Mustjoki\|first9=S\|date=2017-05\|title=Genomic landscape characterization of large granular lymphocyte leukemia with a systems genetics approach\|url=https://www.nature.com/articles/leu201749\|journal=Leukemia\|language=en\|volume=31\|issue=5\|pages=1243–1246\|doi=10.1038/leu.2017.49\|issn=0887-6924\|pmc=5419584\|pmid=28167832}}</ref>
	\|Other <~~sup~~>~~[36]~~</~~sup~~>		\|Other<ref>{{Cite journal\|title=fms related receptor tyrosine kinase 3\|url=https://www.ncbi.nlm.nih.gov/datasets/gene/2322/\|language=en}}</ref>
	\|Rare <~~sup>[44]<~~/~~sup~~>		\|Rare<ref name=":18" />
	\|N/A		\|N/A
	\|WHO		\|WHO
	\|Connects STAT to the MAPK-Ras-ERK pathway and to IL-15 <~~sup>[44]<~~/~~sup~~>		\|Connects STAT to the MAPK-Ras-ERK pathway and to IL-15<ref name=":18" />
	\|-		\|-
	\|PTPN23 <~~sup>[1]<~~/~~sup~~>		\|PTPN23<ref name=":9" />
	\|R641Q <~~sup~~>~~[45]~~</~~sup~~>		\|R641Q<ref name=":19">{{Cite journal\|last=Andersson\|first=Emma I.\|last2=Tanahashi\|first2=Takahiro\|last3=Sekiguchi\|first3=Nodoka\|last4=Gasparini\|first4=Vanessa Rebecca\|last5=Bortoluzzi\|first5=Sabrina\|last6=Kawakami\|first6=Toru\|last7=Matsuda\|first7=Kazuyuki\|last8=Mitsui\|first8=Takeki\|last9=Eldfors\|first9=Samuli\|date=2016-11-17\|title=High incidence of activating STAT5B mutations in CD4-positive T-cell large granular lymphocyte leukemia\|url=https://ashpublications.org/blood/article/128/20/2465/35603/High-incidence-of-activating-STAT5B-mutations-in\|journal=Blood\|language=en\|volume=128\|issue=20\|pages=2465–2468\|doi=10.1182/blood-2016-06-724856\|issn=0006-4971\|pmc=5114490\|pmid=27697773}}</ref>
	\|Other <~~sup~~>~~[37]~~</~~sup~~>		\|Other<ref>{{Cite journal\|title=protein tyrosine phosphatase non-receptor type 23\|url=https://www.ncbi.nlm.nih.gov/datasets/gene/25930/\|language=en}}</ref>
	\|Rare <~~sup>[45]<~~/~~sup~~>		\|Rare<ref name=":19" />
	\|N/A		\|N/A
	\|WHO		\|WHO
	\|Demonstrated in a patient with CD4+ T-LGLL without a STAT5B or STAT3 mutation <~~sup>[45]<~~/~~sup~~>		\|Demonstrated in a patient with CD4+ T-LGLL without a STAT5B or STAT3 mutation<ref name=":19" />
	\|-		\|-
	\|KMT2D <sup>[26]</sup>		\|KMT2D <sup>[26]</sup>

Nicolas.LaScala at 21:00, 16 January 2026

2026-01-16T21:00:18Z

← Older revision		Revision as of 16:00, 16 January 2026
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	STAT5B mutations are more common in CD4+ T-LGLL than in CD8+ T-LGLL <ref name=":14" /><ref>{{Cite journal\|last=Andersson\|first=Emma I.\|last2=Tanahashi\|first2=Takahiro\|last3=Sekiguchi\|first3=Nodoka\|last4=Gasparini\|first4=Vanessa Rebecca\|last5=Bortoluzzi\|first5=Sabrina\|last6=Kawakami\|first6=Toru\|last7=Matsuda\|first7=Kazuyuki\|last8=Mitsui\|first8=Takeki\|last9=Eldfors\|first9=Samuli\|date=2016-11-17\|title=High incidence of activating STAT5B mutations in CD4-positive T-cell large granular lymphocyte leukemia\|url=https://ashpublications.org/blood/article/128/20/2465/35603/High-incidence-of-activating-STAT5B-mutations-in\|journal=Blood\|language=en\|volume=128\|issue=20\|pages=2465–2468\|doi=10.1182/blood-2016-06-724856\|issn=0006-4971\|pmc=5114490\|pmid=27697773}}</ref>		STAT5B mutations are more common in CD4+ T-LGLL than in CD8+ T-LGLL <ref name=":14" /><ref>{{Cite journal\|last=Andersson\|first=Emma I.\|last2=Tanahashi\|first2=Takahiro\|last3=Sekiguchi\|first3=Nodoka\|last4=Gasparini\|first4=Vanessa Rebecca\|last5=Bortoluzzi\|first5=Sabrina\|last6=Kawakami\|first6=Toru\|last7=Matsuda\|first7=Kazuyuki\|last8=Mitsui\|first8=Takeki\|last9=Eldfors\|first9=Samuli\|date=2016-11-17\|title=High incidence of activating STAT5B mutations in CD4-positive T-cell large granular lymphocyte leukemia\|url=https://ashpublications.org/blood/article/128/20/2465/35603/High-incidence-of-activating-STAT5B-mutations-in\|journal=Blood\|language=en\|volume=128\|issue=20\|pages=2465–2468\|doi=10.1182/blood-2016-06-724856\|issn=0006-4971\|pmc=5114490\|pmid=27697773}}</ref>
	\|-		\|-
	\|TNFAIP3 <~~sup>[1]<~~/~~sup~~>		\|TNFAIP3 <ref name=":9" />
	\|Loss of function		\|Loss of function
	Somatic mutations:		Somatic mutations:
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	A717T		A717T

	F127C <~~sup~~>~~[9]~~</~~sup~~>		F127C <ref>{{Cite journal\|last=Johansson\|first=Patricia\|last2=Bergmann\|first2=Anke\|last3=Rahmann\|first3=Sven\|last4=Wohlers\|first4=Inken\|last5=Scholtysik\|first5=René\|last6=Przekopowitz\|first6=Martina\|last7=Seifert\|first7=Marc\|last8=Tschurtschenthaler\|first8=Gertraud\|last9=Webersinke\|first9=Gerald\|date=2016-01-01\|title=Recurrent alterations of TNFAIP 3 (A20) in T-cell large granular lymphocytic leukemia: A20 mutations in T-LGL\|url=https://onlinelibrary.wiley.com/doi/10.1002/ijc.29697\|journal=International Journal of Cancer\|language=en\|volume=138\|issue=1\|pages=121–124\|doi=10.1002/ijc.29697}}</ref>
	\|Other <~~sup~~>[33]</~~sup~~>		\|Other <ref>{{Cite journal\|title=TNFAIP3 TNF alpha induced protein 3 [Homo sapiens (human)] - Gene - NCBI\|url=https://www.ncbi.nlm.nih.gov/gene/7128\|language=en}}</ref>
	\|Recurrent <sup>[46]</sup>		\|Recurrent <sup>[46]</sup>
	\|P,T		\|P,T

Nicolas.LaScala: /* Individual Region Genomic Gain/Loss/LOH */

2026-01-16T20:46:29Z

Individual Region Genomic Gain/Loss/LOH

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Nicolas.LaScala: /* Gene Mutations (SNV/INDEL) */

2026-01-15T04:42:10Z

Gene Mutations (SNV/INDEL)

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Nicolas.LaScala: /* Gene Rearrangements */

2026-01-15T01:00:18Z

Gene Rearrangements

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Nicolas.LaScala: /* Primary Author(s)* */

2026-01-14T22:44:15Z

Primary Author(s)*

@@ Line 12: / Line 12: @@
 *Michelle Don, MD, MS
 ==WHO Classification of Disease==
@@ Line 48: / Line 49: @@
 ==Gene Rearrangements==
+No know chromosomal rearrangements. <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
 {| class="wikitable sortable"
 |-
@@ Line 58: / Line 58: @@
 !Clinical Relevance Details/Other Notes
 |-
-|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
+|N/A||N/A||N/A||N/A
 |<span class="blue-text">EXAMPLE:</span> Common (CML)
 |<span class="blue-text">EXAMPLE:</span> D, P, T
@@ Line 64: / Line 64: @@
 |<span class="blue-text">EXAMPLE:</span>
 The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).
 |-
+|

Bailey.Glen at 17:30, 3 July 2025

2025-07-03T17:30:32Z

← Older revision		Revision as of 12:30, 3 July 2025
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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 21:50, 25 May 2025

2025-05-25T21:50:51Z

← Older revision		Revision as of 16:50, 25 May 2025
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	{\| class="wikitable sortable"		{\| class="wikitable sortable"
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	!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''
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	*Causing constitutive phosphorylation of the mutated proteins, and increased the transcriptional activity of STAT3 in vitro<ref name=":1">Jerez A, Clemente MJ, Makishima H, Koskela H, LeBlanc F, Peng Ng K, Olson T, Przychodzen B, Afable M, Gomez-Segui I, Guinta K. STAT3 mutations unify the pathogenesis of chronic lymphoproliferative disorders of NK cells and T-cell large granular lymphocyte leukemia. Blood, The Journal of the American Society of Hematology. 2012 Oct 11;120(15):3048-57.</ref><ref name=":2">Koskela HL, Eldfors S, Ellonen P, van Adrichem AJ, Kuusanmäki H, Andersson EI, Lagström S, Clemente MJ, Olson T, Jalkanen SE, Majumder MM. Somatic STAT3 mutations in large granular lymphocytic leukemia. New England Journal of Medicine. 2012 May 17;366(20):1905-13.</ref>		*Causing constitutive phosphorylation of the mutated proteins, and increased the transcriptional activity of STAT3 in vitro<ref name=":1">Jerez A, Clemente MJ, Makishima H, Koskela H, LeBlanc F, Peng Ng K, Olson T, Przychodzen B, Afable M, Gomez-Segui I, Guinta K. STAT3 mutations unify the pathogenesis of chronic lymphoproliferative disorders of NK cells and T-cell large granular lymphocyte leukemia. Blood, The Journal of the American Society of Hematology. 2012 Oct 11;120(15):3048-57.</ref><ref name=":2">Koskela HL, Eldfors S, Ellonen P, van Adrichem AJ, Kuusanmäki H, Andersson EI, Lagström S, Clemente MJ, Olson T, Jalkanen SE, Majumder MM. Somatic STAT3 mutations in large granular lymphocytic leukemia. New England Journal of Medicine. 2012 May 17;366(20):1905-13.</ref>
	\|~~'''~~GOF~~'''~~\|\|40-70%<ref name=":2" />		\|GOF\|\|40-70%<ref name=":2" />
	\|		\|
	*17% of patients with STAT3 mutations, had multiple mutations in the STAT3 gene, solely in cytotoxic CD8+ or NK cells.<ref name=":4">Rajala HL, Olson T, Clemente MJ, Lagström S, Ellonen P, Lundan T, Hamm DE, Zaman SA, Marti JM, Andersson EI, Jerez A. The analysis of clonal diversity and therapy responses using STAT3 mutations as a molecular marker in large granular lymphocytic leukemia. haematologica. 2015 Jan 1;100(1):91-9.</ref>		*17% of patients with STAT3 mutations, had multiple mutations in the STAT3 gene, solely in cytotoxic CD8+ or NK cells.<ref name=":4">Rajala HL, Olson T, Clemente MJ, Lagström S, Ellonen P, Lundan T, Hamm DE, Zaman SA, Marti JM, Andersson EI, Jerez A. The analysis of clonal diversity and therapy responses using STAT3 mutations as a molecular marker in large granular lymphocytic leukemia. haematologica. 2015 Jan 1;100(1):91-9.</ref>
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	*Causing constitutive phosphorylation of the mutated proteins, and increased the transcriptional activity of STAT5B in vitro<ref name=":1" /><ref name=":2" />		*Causing constitutive phosphorylation of the mutated proteins, and increased the transcriptional activity of STAT5B in vitro<ref name=":1" /><ref name=":2" />
	*		*
	\|~~'''~~GOF~~'''~~		\|GOF
	\|2%<ref name=":7">Rajala HL, Eldfors S, Kuusanmäki H, Van Adrichem AJ, Olson T, Lagström S, Andersson EI, Jerez A, Clemente MJ, Yan Y, Zhang D. Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia. Blood, The Journal of the American Society of Hematology. 2013 May 30;121(22):4541-50.</ref>		\|2%<ref name=":7">Rajala HL, Eldfors S, Kuusanmäki H, Van Adrichem AJ, Olson T, Lagström S, Andersson EI, Jerez A, Clemente MJ, Yan Y, Zhang D. Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia. Blood, The Journal of the American Society of Hematology. 2013 May 30;121(22):4541-50.</ref>
	\|		\|
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	**A717T		**A717T
	**F127C		**F127C
	\|~~'''~~LOF~~'''~~ (Nonsense mutations)<ref name=":6" />		\|LOF (Nonsense mutations)<ref name=":6" />
	\|Identified in 3/39 patients<ref name=":6" />		\|Identified in 3/39 patients<ref name=":6" />
	\|		\|