Changes

==Definition / Description of Disease==

==Definition / Description of Disease==

This is a distinct entity in the 5th edition World Health Organization (WHO) classification system (https://tumourclassification.iarc.who.int/welcome/).  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>.       

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==

==Synonyms / Terminology==

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.

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==

==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==

==Genes and Main Pathways Involved==