HAEM5:Hairy cell leukaemia: Difference between revisions

<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:Hairy Cell Leukemia]].

*Michael Lack, DO, Shivani Golem, PhD FACMG

*Median age:  58 years, rarely in patients in their 20s

*Males:Females:  4:1

<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref>{{Cite journal|last=Lr|first=Teras|last2=Ce|first2=DeSantis|last3=Jr|first3=Cerhan|last4=Lm|first4=Morton|last5=A|first5=Jemal|last6=Cr|first6=Flowers|date=2016|title=2016 US Lymphoid Malignancy Statistics by World Health Organization Subtypes|url=https://pubmed.ncbi.nlm.nih.gov/27618563/|language=en|pmid=27618563}}</ref></blockquote>

|

*Asymptomatic (incidental finding on complete blood counts)

*B-symptoms (weight loss, fever, night sweats)

*Lymphadenopathy (rare)

|Pancytopenia (monocytopenia is characteristic)

Lymphocytosis (low level)

<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=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":2">{{Cite journal|last=Grever|first=Michael R.|last2=Abdel-Wahab|first2=Omar|last3=Andritsos|first3=Leslie A.|last4=Banerji|first4=Versha|last5=Barrientos|first5=Jacqueline|last6=Blachly|first6=James S.|last7=Call|first7=Timothy G.|last8=Catovsky|first8=Daniel|last9=Dearden|first9=Claire|date=2017|title=Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia|url=https://ashpublications.org/blood/article/129/5/553/36153/Consensus-guidelines-for-the-diagnosis-and|journal=Blood|language=en|volume=129|issue=5|pages=553–560|doi=10.1182/blood-2016-01-689422|issn=0006-4971|pmc=PMC5290982|pmid=27903528}}</ref></blockquote>

*Liver

*Blood (small number)

<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":2" /></blockquote>

<blockquote class="blockedit">{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":2" /></blockquote>

|Positive (B-cell lineage markersl)||CD19, CD20 (bright), CD22, PAX5, FMC7, sIg (bright, monoclonal)

|Positive||CD200 (bright), CD11c, CD103, CD123, CD25, CD72, annexin‐A1, BRAF V600E, phospho-ERK

|Negative||CD5, CD10 (10-20% may be positive), CD23, CD27

<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=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":2" /></blockquote>

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

!chromosome<ref name=":5" /><ref name=":6" />

|33%

|13q

|Loss of RB1, miR-15a, and miR-16-1

|6%

|5

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

!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>

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.}}

*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>.

{| class="wikitable"

!Gene^‡!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism

(LOF/GOF/Other)

!Prevalence<ref name=":1" />

|context dependent<ref name=":8" />

|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.}}

|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>

*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>

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

[[Category:HAEM5]]

[[Category:DISEASE]]

[[Category:Diseases H]]