HAEM5:Chronic lymphocytic leukaemia/small lymphocytic lymphoma: Difference between revisions

==Individual Region Genomic Gain/Loss/LOH==

*Deletion of chromosome 13q14 detected by FISH is the most common cytogenetic abnormality in CLL. The deleted region includes two microRNAs, miR15A and miR16-1<ref name=":4">{{Cite journal|last=Liew|first=Danny|last2=Krum|first2=Henry|date=2002-10|title=The role of aldosterone receptor blockade in the management of cardiovascular disease|url=https://pubmed.ncbi.nlm.nih.gov/12431020|journal=Current Opinion in Investigational Drugs (London, England: 2000)|volume=3|issue=10|pages=1468–1473|issn=1472-4472|pmid=12431020}}</ref>. These microRNAs inhibit the expression of genes involved in apoptosis and cell cycle regulation. Deletion of miR15A and miR16-1 leads to upregulation of BCL2<ref>{{Cite journal|last=Cimmino|first=Amelia|last2=Calin|first2=George Adrian|last3=Fabbri|first3=Muller|last4=Iorio|first4=Marilena V.|last5=Ferracin|first5=Manuela|last6=Shimizu|first6=Masayoshi|last7=Wojcik|first7=Sylwia E.|last8=Aqeilan|first8=Rami I.|last9=Zupo|first9=Simona|date=2005-09-27|title=miR-15 and miR-16 induce apoptosis by targeting BCL2|url=https://pubmed.ncbi.nlm.nih.gov/16166262|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=102|issue=39|pages=13944–13949|doi=10.1073/pnas.0506654102|issn=0027-8424|pmc=1236577|pmid=16166262}}</ref>. Deletion of 13q14 as the sole cytogenetic abnormality is associated with a favorable prognosis. Deletions may be heterozygous or homozygous with a similar prognosis. Individuals with a high percentage of nuclei with 13q deletion (>65%) may have a less favorable prognosis<ref>{{Cite journal|last=Van Dyke|first=Daniel L.|last2=Shanafelt|first2=Tait D.|last3=Call|first3=Timothy G.|last4=Zent|first4=Clive S.|last5=Smoley|first5=Stephanie A.|last6=Rabe|first6=Kari G.|last7=Schwager|first7=Susan M.|last8=Sonbert|first8=Jessica C.|last9=Slager|first9=Susan L.|date=2010-02|title=A comprehensive evaluation of the prognostic significance of 13q deletions in patients with B-chronic lymphocytic leukaemia|url=https://pubmed.ncbi.nlm.nih.gov/19895615|journal=British Journal of Haematology|volume=148|issue=4|pages=544–550|doi=10.1111/j.1365-2141.2009.07982.x|issn=1365-2141|pmc=2866061|pmid=19895615}}</ref>

'''CLL Tables''' - A list of clinically significant and/or recurrent CNAs and CN-LOH with potential or strong diagnostic, prognostic and treatment implications in CLL. Table derived from Chun et al., 2018 [<ref>{{Cite journal|last=K|first=Chun|last2=Gd|first2=Wenger|last3=A|first3=Chaubey|last4=Dp|first4=Dash|last5=R|first5=Kanagal-Shamanna|last6=S|first6=Kantarci|last7=R|first7=Kolhe|last8=Dl|first8=Van Dyke|last9=L|first9=Wang|date=2018|title=Assessing copy number aberrations and copy-neutral loss-of-heterozygosity across the genome as best practice: An evidence-based review from the Cancer Genomics Consortium (CGC) working group for chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/30554732/|language=en|pmid=30554732}}</ref>] with permission from Cancer Genetics. See [[CLL Tables: Regions of Recurrent Copy Number Change and CN-LOH]].

|Yes

|No

|-

|11

|Yes

|No

|-

|17

|Yes

|Yes

|}

==Characteristic Chromosomal Patterns==

<br />

|-

|Other (may be important for follicular differentiation and possible cell fate selection within the follicle)

|5-12.3%

|No

|Yes

|intermediate risk<ref name=":7">{{Cite journal|last=Jeromin|first=S.|last2=Weissmann|first2=S.|last3=Haferlach|first3=C.|last4=Dicker|first4=F.|last5=Bayer|first5=K.|last6=Grossmann|first6=V.|last7=Alpermann|first7=T.|last8=Roller|first8=A.|last9=Kohlmann|first9=A.|date=2014-01|title=SF3B1 mutations correlated to cytogenetics and mutations in NOTCH1, FBXW7, MYD88, XPO1 and TP53 in 1160 untreated CLL patients|url=https://pubmed.ncbi.nlm.nih.gov/24113472|journal=Leukemia|volume=28|issue=1|pages=108–117|doi=10.1038/leu.2013.263|issn=1476-5551|pmid=24113472}}</ref><ref name=":8">{{Cite journal|last=Rossi|first=Davide|last2=Rasi|first2=Silvia|last3=Spina|first3=Valeria|last4=Bruscaggin|first4=Alessio|last5=Monti|first5=Sara|last6=Ciardullo|first6=Carmela|last7=Deambrogi|first7=Clara|last8=Khiabanian|first8=Hossein|last9=Serra|first9=Roberto|date=2013-02-21|title=Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/23243274|journal=Blood|volume=121|issue=8|pages=1403–1412|doi=10.1182/blood-2012-09-458265|issn=1528-0020|pmc=3578955|pmid=23243274}}</ref>

|-

|Other (part of the spliceosome machinery)

|9-10%

|Del(11q)

|No

|Yes

|intermediate risk<ref name=":7" /><ref name=":8" />

|-

|Tumor suppressor gene

|7.1%

|High risk<ref name=":7" /><ref name=":8" />

|-

|Tumor suppressor gene

|7.2%

!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome

|-

|Notch signaling

|Abnormally stabilized Notch signaling<ref>{{Cite journal|last=Mesini|first=Nicolò|last2=Fiorcari|first2=Stefania|last3=Atene|first3=Claudio Giacinto|last4=Maffei|first4=Rossana|last5=Potenza|first5=Leonardo|last6=Luppi|first6=Mario|last7=Marasca|first7=Roberto|date=2022|title=Role of Notch2 pathway in mature B cell malignancies|url=https://pubmed.ncbi.nlm.nih.gov/36686759|journal=Frontiers in Oncology|volume=12|pages=1073672|doi=10.3389/fonc.2022.1073672|issn=2234-943X|pmc=9846264|pmid=36686759}}</ref>

|-

|DNA damage response

|Cell proliferation and reduced response to cytotoxic chemotherapy<ref>{{Cite journal|last=Aitken|first=Marisa J. L.|last2=Lee|first2=Hun J.|last3=Post|first3=Sean M.|date=2019|title=Emerging treatment options for patients with p53-pathway-deficient CLL|url=https://pubmed.ncbi.nlm.nih.gov/31839919|journal=Therapeutic Advances in Hematology|volume=10|pages=2040620719891356|doi=10.1177/2040620719891356|issn=2040-6207|pmc=6896129|pmid=31839919}}</ref>

|-

|NF-kB signaling

|Activation of non-canonical NF-kB signaling<ref name=":9" />