HAEM5:Hairy cell leukaemia: Difference between revisions

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

<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:Hairy Cell Leukemia]].

==WHO Classification of Disease==

|Book

|Haematolymphoid Tumours (5th ed.)

|Category

|B-cell lymphoid proliferations and lymphomas

|Family

|Mature B-cell neoplasms

|Type

|Splenic B-cell lymphomas and leukaemias

|Subtype(s)

|Hairy cell leukaemia

==Related Terminology==

 

!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)

!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)

!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T

!Established Clinical Significance Per Guidelines - Yes or No (Source)

|<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)

|<span class="blue-text">EXAMPLE:</span> Common (CML)

|<span class="blue-text">EXAMPLE:</span> D, P, T

|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span> ''CIC''

|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''

|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.

|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)

|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)

|<span class="blue-text">EXAMPLE:</span> D

|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.

|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.

|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)

|<span class="blue-text">EXAMPLE:</span> D, P, T

|

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|}

*Single case report of IGH-BRAF fusion positive, BRAF p.Val600Glu mutation negative HCL<ref name=":3" />

*Single case report of IGH-CCND1 fusion positive, BRAF p.Val600Glu mutation positive HCL<ref name=":4" />

<blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>

<blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:

* Gene Mutations (SNV/INDEL)}}</blockquote>

|May be useful when immunophenotype is equivocal; Excludes [[HAEM5:Splenic B-cell lymphoma/leukaemia with prominent nucleoli|HCLv]]

Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>

!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

!Established Clinical Significance Per Guidelines - Yes or No (Source)

!Clinical Relevance Details/Other Notes

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span> Loss

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span> D, P

|<span class="blue-text">EXAMPLE:</span> No

|<span class="blue-text">EXAMPLE:</span>

Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add references).

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span> Gain

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span> D, P, T

|

|<span class="blue-text">EXAMPLE:</span>

|9-21%

|}  

<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>

!chromosome<ref name=":5">{{Cite journal|last=Durham|first=Benjamin H.|last2=Getta|first2=Bartlomiej|last3=Dietrich|first3=Sascha|last4=Taylor|first4=Justin|last5=Won|first5=Helen|last6=Bogenberger|first6=James M.|last7=Scott|first7=Sasinya|last8=Kim|first8=Eunhee|last9=Chung|first9=Young Rock|date=2017|title=Genomic analysis of hairy cell leukemia identifies novel recurrent genetic alterations|url=https://www.ncbi.nlm.nih.gov/pubmed/28801450|journal=Blood|volume=130|issue=14|pages=1644–1648|doi=10.1182/blood-2017-01-765107|issn=1528-0020|pmc=5630011|pmid=28801450}}</ref><ref name=":6">{{Cite journal|last=A|first=Nordgren|last2=M|first2=Corcoran|last3=A|first3=Sääf|last4=A|first4=Bremer|last5=Hc|first5=Kluin-Nelemans|last6=J|first6=Schoumans|last7=D|first7=Grandér|date=2010|title=Characterisation of Hairy Cell Leukaemia by Tiling Resolution Array-Based Comparative Genome Hybridisation: A Series of 13 Cases and Review of the Literature|url=https://pubmed.ncbi.nlm.nih.gov/19682064/|language=en|pmid=19682064}}</ref>

!Molecular Pathogenesis

Common >20%, Recurrent 5-20% or Rare <5% (Disease)

!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T

!Established Clinical Significance Per Guidelines - Yes or No (Source)

!Clinical Relevance Details/Other Notes

|<span class="blue-text">EXAMPLE:</span>

|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

|

|-

|<span class="blue-text">EXAMPLE:</span>

IGHV4-34 (Immunoglobulin heavy chain variable segment) utilization is seen only in 10%<ref name=":0" /> of HCL but has predictive and prognostic implications<ref name=":7" />.

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

*IGHV4-34 (Immunoglobulin heavy chain variable segment) utilization is seen only in 10%<ref name=":0" /> of HCL but has predictive and prognostic implications<ref name=":7">{{Cite journal|last=Arons|first=Evgeny|last2=Kreitman|first2=Robert J.|date=2011|title=Molecular variant of hairy cell leukemia with poor prognosis|url=https://www.ncbi.nlm.nih.gov/pubmed/21599610|journal=Leukemia & Lymphoma|volume=52 Suppl 2|pages=99–102|doi=10.3109/10428194.2011.565841|issn=1029-2403|pmid=21599610}}</ref>.

|<span class="blue-text">EXAMPLE:</span> Oncogene

|<span class="blue-text">EXAMPLE:</span> T

|<span class="blue-text">EXAMPLE:</span> Yes (NCCN)

|<span class="blue-text">EXAMPLE:</span> Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references).

|<span class="blue-text">EXAMPLE:</span> ''TP53''; Variable LOF mutations

|<span class="blue-text">EXAMPLE:</span> >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer.

|<span class="blue-text">EXAMPLE:</span> Common (melanoma)

|}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.

{| class="wikitable"

|Tumor Suppressor

|CREBBP

|LOF

^‡Specific mutations in these genes can be found in [https://www.cbioportal.org/ cBioPortal] and [https://cancer.sanger.ac.uk/cosmic COSMIC].

'''*'''The WHO states that BRAF p.Val600Glu is detected in virtually all cases and notes that the classification of B-cell leukemias that are immunophenotypically and morphologically classified as HCL but lack BRAF activating mutations (but instead have MAP2K1 activating mutations and use the IGHV4-34 gene segment) is uncertain.  These seem to be more similar molecularly and clinically to [[HAEM5:Splenic B-cell lymphoma/leukaemia with prominent nucleoli|HCLv]].

*BRAF p.Val600Glu and MAP2K1 account for the primary oncogene drivers in the majority of HCL (~95%)

*BRAF p.Val600Glu (p.V600E) accounts for the majority of BRAF mutations, but other have been reported<ref name=":9" />

*HCLs that utilize the IGVH4-34 segment lack BRAF p.Val600Glu mutations<ref name=":10" /> and instead harbor MAP2K1 mutations in most cases<ref name=":11" />

<blockquote class="blockedit">{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}</blockquote>

|context dependent<ref name=":8">{{Cite journal|last=Wang|first=Chunmei|last2=Li|first2=Liang|last3=Duan|first3=Qiuhui|last4=Wang|first4=Qingqing|last5=Chen|first5=Jinlian|date=2017|title=Krüppel-like factor 2 suppresses human gastric tumorigenesis through inhibiting PTEN/AKT signaling|url=https://www.ncbi.nlm.nih.gov/pubmed/29245984|journal=Oncotarget|volume=8|issue=59|pages=100358–100370|doi=10.18632/oncotarget.22229|issn=1949-2553|pmc=5725026|pmid=29245984}}</ref>

'''*'''The WHO states that BRAF p.Val600Glu is detected in virtually all cases and notes that the classification of B-cell leukemias that are immunophenotypically and morphologically classified as HCL but lack BRAF activating mutations (but instead have MAP2K1 activating mutations and use the IGHV4-34 gene segment) is uncertain.  These seem to be more similar molecularly and clinically to [[HAEM5:Splenic B-cell lymphoma/leukaemia with prominent nucleoli|HCLv]].

*BRAF p.Val600Glu (p.V600E) accounts for the majority of BRAF mutations, but other have been reported<ref name=":9">{{Cite journal|last=Tschernitz|first=Sebastian|last2=Flossbach|first2=Lucia|last3=Bonengel|first3=Margrit|last4=Roth|first4=Sabine|last5=Rosenwald|first5=Andreas|last6=Geissinger|first6=Eva|date=2014|title=Alternative BRAF mutations in BRAF V600E-negative hairy cell leukaemias|url=https://www.ncbi.nlm.nih.gov/pubmed/24433452|journal=British Journal of Haematology|volume=165|issue=4|pages=529–533|doi=10.1111/bjh.12735|issn=1365-2141|pmid=24433452}}</ref>

*HCLs that utilize the IGVH4-34 segment lack BRAF p.Val600Glu mutations<ref name=":10">{{Cite journal|last=Xi|first=Liqiang|last2=Arons|first2=Evgeny|last3=Navarro|first3=Winnifred|last4=Calvo|first4=Katherine R.|last5=Stetler-Stevenson|first5=Maryalice|last6=Raffeld|first6=Mark|last7=Kreitman|first7=Robert J.|date=2012|title=Both variant and IGHV4-34-expressing hairy cell leukemia lack the BRAF V600E mutation|url=https://www.ncbi.nlm.nih.gov/pubmed/22210875|journal=Blood|volume=119|issue=14|pages=3330–3332|doi=10.1182/blood-2011-09-379339|issn=1528-0020|pmc=3321859|pmid=22210875}}</ref> and instead harbor MAP2K1 mutations in most cases<ref name=":11">{{Cite journal|last=Waterfall|first=Joshua J.|last2=Arons|first2=Evgeny|last3=Walker|first3=Robert L.|last4=Pineda|first4=Marbin|last5=Roth|first5=Laura|last6=Killian|first6=J. Keith|last7=Abaan|first7=Ogan D.|last8=Davis|first8=Sean R.|last9=Kreitman|first9=Robert J.|date=2014|title=High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias|url=https://www.ncbi.nlm.nih.gov/pubmed/24241536|journal=Nature Genetics|volume=46|issue=1|pages=8–10|doi=10.1038/ng.2828|issn=1546-1718|pmc=3905739|pmid=24241536}}</ref>

!Molecular feature!!Pathway!!Pathophysiologic outcome

|BRAF & MAP2K1 activating mutations

|MAPK signaling

|Increased cell growth and proliferation

|CDKN1B inactivating mutations

(IGH-CCND1 fusion, 1 report<ref name=":4" />)

|Cell cycle regulation

|Unregulated cell division

|KMT2C & ARID1A inactivating mutaitons

|Histone modification, chromatin remodeling

|Abnormal gene expression program

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

*Small lymphoid cells; Abundant pale blue-grey lacey cytoplasm; Ovoid nuclei ± indentation or folding; Inconspicuous nucleoli; Circumferential hairy projections (smear preparations); "Fried egg" appearance of cells (tissue sections); Marrow (reticulin) fibrosis

 

The <u>immunophenotype</u><ref name=":1" /><ref name=":2" /> of this disease is detailed below:

 

 

 

 

*[[HAEM5:Splenic B-cell lymphoma/leukaemia with prominent nucleoli]]

*[[HAEM5:Splenic diffuse red pulp small B-cell lymphoma]]

(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 />

<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.

 

 

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[[Category:Diseases H]]