Changes

254 bytes added , 16:37, 20 December 2023

Line 22: Line 22:

==Definition / Description of Disease==

−

This is a distinct entity in the ~~2016~~ World Health Organization (WHO) classification system<ref name=":1">Campo E, et al., (2017). Chronic lymphocytic leukemia/small lymphocytic lymphoma, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. Revised 4th Edition. IARC Press: Lyon, France, p216-221.</ref>. Chronic Lymphocytic Leukemia (CLL) is a chronic lymphoproliferative disorder characterized by monoclonal B cell proliferation. CLL is defined by the presence of >5x109/L monoclonal B-cells in the peripheral blood. Cells are small, mature appearing lymphocytes with light chain restriction by flow cytometry. The term small lymphocytic lymphoma (SLL) is used for cases with <5x109/L circulating monoclonal B-cells and documented nodal, splenic, or other extramedullary involvement<ref name=":2">{{Cite journal|last=Hallek|first=Michael|last2=Cheson|first2=Bruce D.|last3=Catovsky|first3=Daniel|last4=Caligaris-Cappio|first4=Federico|last5=Dighiero|first5=Guillaume|last6=Döhner|first6=Hartmut|last7=Hillmen|first7=Peter|last8=Keating|first8=Michael J.|last9=Montserrat|first9=Emili|date=2008-06-15|title=Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines|url=https://pubmed.ncbi.nlm.nih.gov/18216293|journal=Blood|volume=111|issue=12|pages=5446–5456|doi=10.1182/blood-2007-06-093906|issn=1528-0020|pmc=2972576|pmid=18216293}}</ref>.

+

This is a distinct entity in the [https://tumourclassification.iarc.who.int/welcome/ 5th edition World Health Organization (WHO) classification system]. It was also a distinct entity in the 2016 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues revised 4th edition<ref name=":1">Campo E, et al., (2017). Chronic lymphocytic leukemia/small lymphocytic lymphoma, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. Revised 4th Edition. IARC Press: Lyon, France, p216-221.</ref>. Chronic Lymphocytic Leukemia (CLL) is a chronic lymphoproliferative disorder characterized by monoclonal B cell proliferation. CLL is defined by the presence of >5x109/L monoclonal B-cells in the peripheral blood. Cells are small, mature appearing lymphocytes with light chain restriction by flow cytometry. The term small lymphocytic lymphoma (SLL) is used for cases with <5x109/L circulating monoclonal B-cells and documented nodal, splenic, or other extramedullary involvement<ref name=":2">{{Cite journal|last=Hallek|first=Michael|last2=Cheson|first2=Bruce D.|last3=Catovsky|first3=Daniel|last4=Caligaris-Cappio|first4=Federico|last5=Dighiero|first5=Guillaume|last6=Döhner|first6=Hartmut|last7=Hillmen|first7=Peter|last8=Keating|first8=Michael J.|last9=Montserrat|first9=Emili|date=2008-06-15|title=Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines|url=https://pubmed.ncbi.nlm.nih.gov/18216293|journal=Blood|volume=111|issue=12|pages=5446–5456|doi=10.1182/blood-2007-06-093906|issn=1528-0020|pmc=2972576|pmid=18216293}}</ref>.

==Synonyms / Terminology==

Line 127: Line 127:

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

−

*Approximately 80% of CLL patients have a cytogenetic abnormality detectable by fluorescence in situ hybridization (FISH)

+

*Approximately 80% of CLL patients have a cytogenetic abnormality detectable by fluorescence ''in situ'' hybridization (FISH)

−

*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>

+

*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>

−

*Deletion of 17p, which includes TP53, is associated with poor prognosis and resistance to standard chemotherapy regimens<ref name=":5">{{Cite journal|last=Döhner|first=H.|last2=Stilgenbauer|first2=S.|last3=Benner|first3=A.|last4=Leupolt|first4=E.|last5=Kröber|first5=A.|last6=Bullinger|first6=L.|last7=Döhner|first7=K.|last8=Bentz|first8=M.|last9=Lichter|first9=P.|date=2000-12-28|title=Genomic aberrations and survival in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/11136261|journal=The New England Journal of Medicine|volume=343|issue=26|pages=1910–1916|doi=10.1056/NEJM200012283432602|issn=0028-4793|pmid=11136261}}</ref>.

+

*Deletion of 17p, which includes ''TP53'', is associated with poor prognosis and resistance to standard chemotherapy regimens<ref name=":5">{{Cite journal|last=Döhner|first=H.|last2=Stilgenbauer|first2=S.|last3=Benner|first3=A.|last4=Leupolt|first4=E.|last5=Kröber|first5=A.|last6=Bullinger|first6=L.|last7=Döhner|first7=K.|last8=Bentz|first8=M.|last9=Lichter|first9=P.|date=2000-12-28|title=Genomic aberrations and survival in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/11136261|journal=The New England Journal of Medicine|volume=343|issue=26|pages=1910–1916|doi=10.1056/NEJM200012283432602|issn=0028-4793|pmid=11136261}}</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]].

Line 147: Line 147:

|Yes

|No

−

|Most common cytogenetic abnormality. Isolated 13q- is associated with favorable prognosis<ref name=":4" />.

+

|Most common cytogenetic abnormality. Isolated 13q deletion is associated with favorable prognosis<ref name=":4" />.

|-

|11

Line 156: Line 156:

|Yes

|No

−

|Deletion of ATM. Associated with a poor prognosis.

+

|Deletion of ''ATM''. Associated with a poor prognosis.

|-

|17

Line 165: Line 165:

|Yes

−

|Deletion of TP53. Patients with 17p deletion show resistance to genotoxic chemotherapies. TP53 deletion is associated with a poor prognosis<ref name=":5" />.

+

|Deletion of ''TP53''. Patients with 17p deletion show resistance to genotoxic chemotherapies. ''TP53'' deletion is associated with a poor prognosis<ref name=":5" />.

|}

==Characteristic Chromosomal Patterns==

Line 183: Line 183:

|Yes

|No

−

|Can also be detected in the homozygous state. Biallelic deletions are often cryptic and not cytogenetically visible<ref>{{Cite journal|last=Migliazza|first=A.|last2=Bosch|first2=F.|last3=Komatsu|first3=H.|last4=Cayanis|first4=E.|last5=Martinotti|first5=S.|last6=Toniato|first6=E.|last7=Guccione|first7=E.|last8=Qu|first8=X.|last9=Chien|first9=M.|date=2001-04-01|title=Nucleotide sequence, transcription map, and mutation analysis of the 13q14 chromosomal region deleted in B-cell chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/11264177|journal=Blood|volume=97|issue=7|pages=2098–2104|doi=10.1182/blood.v97.7.2098|issn=0006-4971|pmid=11264177}}</ref>. 13q deletion as the sole abnormality is typically associated with a good prognosis, however, CLL with a high percentage of nuclei with 13q deletion may have a more aggressive clinical course<ref>{{Cite journal|last=Dal Bo|first=Michele|last2=Rossi|first2=Francesca Maria|last3=Rossi|first3=Davide|last4=Deambrogi|first4=Clara|last5=Bertoni|first5=Francesco|last6=Del Giudice|first6=Ilaria|last7=Palumbo|first7=Giuseppe|last8=Nanni|first8=Mauro|last9=Rinaldi|first9=Andrea|date=2011-08|title=13q14 deletion size and number of deleted cells both influence prognosis in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/21563234|journal=Genes, Chromosomes & Cancer|volume=50|issue=8|pages=633–643|doi=10.1002/gcc.20885|issn=1098-2264|pmid=21563234}}</ref>

+

|Can also be detected in the homozygous state. Biallelic deletions are often cryptic and not cytogenetically visible<ref>{{Cite journal|last=Migliazza|first=A.|last2=Bosch|first2=F.|last3=Komatsu|first3=H.|last4=Cayanis|first4=E.|last5=Martinotti|first5=S.|last6=Toniato|first6=E.|last7=Guccione|first7=E.|last8=Qu|first8=X.|last9=Chien|first9=M.|date=2001-04-01|title=Nucleotide sequence, transcription map, and mutation analysis of the 13q14 chromosomal region deleted in B-cell chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/11264177|journal=Blood|volume=97|issue=7|pages=2098–2104|doi=10.1182/blood.v97.7.2098|issn=0006-4971|pmid=11264177}}</ref>. 13q deletion as the sole abnormality is typically associated with a good prognosis, however, CLL with a high percentage of nuclei with 13q deletion may have a more aggressive clinical course<ref>{{Cite journal|last=Dal Bo|first=Michele|last2=Rossi|first2=Francesca Maria|last3=Rossi|first3=Davide|last4=Deambrogi|first4=Clara|last5=Bertoni|first5=Francesco|last6=Del Giudice|first6=Ilaria|last7=Palumbo|first7=Giuseppe|last8=Nanni|first8=Mauro|last9=Rinaldi|first9=Andrea|date=2011-08|title=13q14 deletion size and number of deleted cells both influence prognosis in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/21563234|journal=Genes, Chromosomes & Cancer|volume=50|issue=8|pages=633–643|doi=10.1002/gcc.20885|issn=1098-2264|pmid=21563234}}</ref>

|-

|11q22.3 deletion

Line 195: Line 195:

|Unknown

|No

−

|Conflicting evidence on prognostic significance. As a sole abnormality may be associated with low risk. Associated with intermediate risk if NOTCH1 mutation is present<ref name=":8" />

+

|Conflicting evidence on prognostic significance. As a sole abnormality may be associated with low risk. Associated with intermediate risk if ''NOTCH1'' mutation is present<ref name=":8" />

|-

|6q21 deletion

Line 218: Line 218:

*IGHV genes are mutated in 50-70% of cases and unmutated in 30-50%.

−

*Unmutated IGHV genes have been shown to have a poorer prognosis, along with TP53, BIRC3, NOTCH1, and SF3B1 mutations.

+

*Unmutated IGHV genes have been shown to have a poorer prognosis, along with ''TP53'', ''BIRC3'', ''NOTCH1'', and ''SF3B1'' mutations.

{| class="wikitable sortable"

Line 239: Line 239:

|-

−

|NOTCH1; frameshift, nonsense, and missense mutations

+

|''NOTCH1''; frameshift, nonsense, and missense mutations

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

|5-12.3%

−

|FBXW7 mutation and trisomy 12

+

|''FBXW7'' mutation and trisomy 12

−

|SF3B1 mutation

+

|''SF3B1'' mutation

|No

|Yes

Line 249: Line 249:

|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>

|-

−

|SF3B1; missense (most)

+

|''SF3B1''; missense (most)

|Other (part of the spliceosome machinery)

|9-10%

|Del(11q)

−

|NOTCH1 and FBXW7 mutations

+

|''NOTCH1'' and ''FBXW7'' mutations

|No

|Yes

Line 259: Line 259:

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

|-

−

|TP53; missense (most)

+

|''TP53''; missense (most)

|Tumor suppressor gene

|7.1%

Line 269: Line 269:

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

|-

−

|BIRC3; frameshift and nonsense

+

|''BIRC3''; frameshift and nonsense

|Tumor suppressor gene

|7.2%

Line 281: Line 281:

Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

==Epigenomic Alterations==

−

Whole genome methylation studies have identified three epigenetic subgroups of CLL<ref name=":10">{{Cite journal|last=Queirós|first=A. C.|last2=Villamor|first2=N.|last3=Clot|first3=G.|last4=Martinez-Trillos|first4=A.|last5=Kulis|first5=M.|last6=Navarro|first6=A.|last7=Penas|first7=E. M. M.|last8=Jayne|first8=S.|last9=Majid|first9=A.|date=2015-03|title=A B-cell epigenetic signature defines three biologic subgroups of chronic lymphocytic leukemia with clinical impact|url=https://pubmed.ncbi.nlm.nih.gov/25151957|journal=Leukemia|volume=29|issue=3|pages=598–605|doi=10.1038/leu.2014.252|issn=1476-5551|pmid=25151957}}</ref> ~~[PMID: 25151957]~~. These subgroups are related to different stages of B-cell maturation and include naïve B-cell like, intermediate, and memory B-cell like CLL. Naïve B-cell like epigenetic subgroup mainly has unmutated IGHV, whereas the memory B-like subgroup mainly have mutated IGHV genes. The intermediate epigenetic subgroup was also found to have mainly mutated IGHV, however, is associated with a worse prognosis than the memory B-like subgroup. The epigenetic classification was found to be an independent prognostic factor for time to first treatment<ref name=":10" /><ref>{{Cite journal|last=Oakes|first=Christopher C.|last2=Seifert|first2=Marc|last3=Assenov|first3=Yassen|last4=Gu|first4=Lei|last5=Przekopowitz|first5=Martina|last6=Ruppert|first6=Amy S.|last7=Wang|first7=Qi|last8=Imbusch|first8=Charles D.|last9=Serva|first9=Andrius|date=2016-03|title=DNA methylation dynamics during B cell maturation underlie a continuum of disease phenotypes in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/26780610|journal=Nature Genetics|volume=48|issue=3|pages=253–264|doi=10.1038/ng.3488|issn=1546-1718|pmc=4963005|pmid=26780610}}</ref>.

+

Whole genome methylation studies have identified three epigenetic subgroups of CLL<ref name=":10">{{Cite journal|last=Queirós|first=A. C.|last2=Villamor|first2=N.|last3=Clot|first3=G.|last4=Martinez-Trillos|first4=A.|last5=Kulis|first5=M.|last6=Navarro|first6=A.|last7=Penas|first7=E. M. M.|last8=Jayne|first8=S.|last9=Majid|first9=A.|date=2015-03|title=A B-cell epigenetic signature defines three biologic subgroups of chronic lymphocytic leukemia with clinical impact|url=https://pubmed.ncbi.nlm.nih.gov/25151957|journal=Leukemia|volume=29|issue=3|pages=598–605|doi=10.1038/leu.2014.252|issn=1476-5551|pmid=25151957}}</ref>. These subgroups are related to different stages of B-cell maturation and include naïve B-cell like, intermediate, and memory B-cell like CLL. Naïve B-cell like epigenetic subgroup mainly has unmutated IGHV, whereas the memory B-like subgroup mainly have mutated IGHV genes. The intermediate epigenetic subgroup was also found to have mainly mutated IGHV, however, is associated with a worse prognosis than the memory B-like subgroup. The epigenetic classification was found to be an independent prognostic factor for time to first treatment<ref name=":10" /><ref>{{Cite journal|last=Oakes|first=Christopher C.|last2=Seifert|first2=Marc|last3=Assenov|first3=Yassen|last4=Gu|first4=Lei|last5=Przekopowitz|first5=Martina|last6=Ruppert|first6=Amy S.|last7=Wang|first7=Qi|last8=Imbusch|first8=Charles D.|last9=Serva|first9=Andrius|date=2016-03|title=DNA methylation dynamics during B cell maturation underlie a continuum of disease phenotypes in chronic lymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/26780610|journal=Nature Genetics|volume=48|issue=3|pages=253–264|doi=10.1038/ng.3488|issn=1546-1718|pmc=4963005|pmid=26780610}}</ref>.

==Genes and Main Pathways Involved==

Line 288: Line 288:

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

|-

−

|NOTCH1; PEST domain truncation

+

|''NOTCH1''; PEST domain truncation

|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>

|-

−

|TP53; deletion and mutations

+

|''TP53''; deletion and mutations

|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>

|-

−

|BIRC3; mutations

+

|''BIRC3''; mutations

|NF-kB signaling

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

Line 314: Line 314:

==Links==

−

~~[[Monoclonal B-cell Lymphocytosis]]~~

+

Not Applicable

==References==

Jennelleh

Bureaucrats, Editors, Administrators

3,883

edits

Changes

HAEM5:Chronic lymphocytic leukaemia/small lymphocytic lymphoma (view source)

Revision as of 16:37, 20 December 2023