Compendium of Cancer Genome Aberrations

HAEM5:Chronic neutrophilic leukaemia: Difference between revisions

[checked revision][checked revision]
← Older editNewer edit →
VisualWikitext
No edit summary
Removed old template contents
Line 1: Line 1:
{{DISPLAYTITLE:Chronic neutrophilic leukaemia}}
{{DISPLAYTITLE:Chronic neutrophilic leukaemia}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]


{{Under Construction}}
{{Under Construction}}


<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:Chronic Neutrophilic Leukemia (CNL)]].
<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:Chronic Neutrophilic Leukemia (CNL)]].
}}</blockquote>
}}</blockquote>


Line 41: Line 42:
|}
|}


==Definition / Description of Disease==
Chronic neutrophilic leukemia (CNL) is a rare heterogeneous BCR/ABL1-negative member of the WHO myeloproliferative neoplasm (MPN) category, which presents with neutrophilia lacking dysplastic features.  Diagnostic criteria include sustained increased white blood cells in the peripheral blood for more than 3 months, with a predominance of band and segmented forms equal to or in excess of 25 x10<sup>9</sup>/L.<ref name=":0" />  The bone marrow is hypercellular with elevated myeloid to erythroid ratio, due to increase in neutrophilic granulocyte proliferation, with normal maturation (>80% mature forms of neutrophils and <10% neutrophil precursors) and rare (<5%) of nucleated cells represented by myeloblasts.  This disease is also associated with hepatosplenomegaly, but can affect other tissues.
Diagnosis is made after exclusion of reactive neutrophilia (especially due to plasma cell neoplasms), atypical CML and of other myeloproliferative neoplasms ([[HAEM5:Chronic myeloid leukaemia|BCR-ABL1- positive Chronic Myeloid Leukemia]], [[HAEM5:Polycythaemia vera|Polycythemia Vera]], [[HAEM5:Essential thrombocythaemia|Essential Thrombocythemia]] and [[HAEM5:Primary myelofibrosis|Primary Myelofibrosis]]) and and myelodysplastic syndrome/myeloproliferative neoplasms.<ref name=":0" /><ref name=":3">{{Cite journal|last=Szuber|first=Natasha|last2=Elliott|first2=Michelle|last3=Tefferi|first3=Ayalew|date=02 2020|title=Chronic neutrophilic leukemia: 2020 update on diagnosis, molecular genetics, prognosis, and management|url=https://pubmed.ncbi.nlm.nih.gov/31769070|journal=American Journal of Hematology|volume=95|issue=2|pages=212–224|doi=10.1002/ajh.25688|issn=1096-8652|pmid=31769070}}</ref><ref name=":4" />  Previous use of G-CSF and leukaemogenic drugs (busulphan, melphalan) must also be excluded.
Mutations in ''CSF3R'' (colony-stimulating factor 3 receptor) are present in the majority of CNL cases and are part of diagnostic criteria. Genetic rearrangement for ''PDGFRA'', ''PDGFRB'', ''FGFR1'', and ''PCM1''-''JAK2'' fusion must be absent.<ref name=":0">Bain BJ, et al., (2017). Chronic Neutrophilic Leukaemia, 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. IARC Press: Lyon, France, p37-38.</ref>
==Synonyms / Terminology==
CNL
==Epidemiology / Prevalence==
CNL is a rare disease with the true incidence being unknown.  While >200 cases were previously reported, three quarters to half of these do not meet current guidelines for a diagnosis of chronic neutrophilic leukemia<ref name=":0" /><ref name=":1">{{Cite journal|last=N|first=Szuber|last2=A|first2=Tefferi|date=2018|title=Chronic neutrophilic leukemia: new science and new diagnostic criteria|url=https://pubmed.ncbi.nlm.nih.gov/29440636/|language=en|doi=10.1038/s41408-018-0049-8|pmc=PMC5811432|pmid=29440636}}</ref>  Evidence suggests that CNL is extremely rare with one report investigating chronic leukemias of myeloid origin finding less than 1/660 cases meeting criteria for establishing the diagnosis.<ref name=":4" /><ref name=":5">{{Cite journal|last=Elliott|first=M. A.|last2=Hanson|first2=C. A.|last3=Dewald|first3=G. W.|last4=Smoley|first4=S. A.|last5=Lasho|first5=T. L.|last6=Tefferi|first6=A.|date=2005-02|title=WHO-defined chronic neutrophilic leukemia: a long-term analysis of 12 cases and a critical review of the literature|url=https://pubmed.ncbi.nlm.nih.gov/15549147|journal=Leukemia|volume=19|issue=2|pages=313–317|doi=10.1038/sj.leu.2403562|issn=0887-6924|pmid=15549147}}</ref>  
Differential diagnosis of CNL includes neutrophilic leukemoid reaction associated with secretion of granulocyte stimulating factor by plasma cells in Multiple Myeloma or MGUS. Median age at presentation is 66 years old, with a nearly equal, slightly higher female to male prevalence.
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
{| class="wikitable"
|'''Signs and Symptoms'''
|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
<span class="blue-text">EXAMPLE:</span> Fatigue
<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
|-
|'''Laboratory Findings'''
|<span class="blue-text">EXAMPLE:</span> Cytopenias
<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}</blockquote>
Most patients are asymptomatic, but sometimes present with fatigue. Constitutional symptoms may be present at diagnosis, including weight loss, and night sweats. Sometimes bruising, pruritus, or gout. A common clinical manifestation is hepatosplenomegaly.
Blood analysis can show elevated values for LDH, leukocyte alkaline phosphatase (LAP), serum vitamin B12, and uric acid.
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
==Sites of Involvement==
Peripheral blood and bone marrow involvement are consistently present.  The spleen and liver are two of the most involved extramedullary sites with splenomegaly and/or hepatomegaly resulting from infiltrating neutrophils.<ref name=":0" /><ref name=":3" /><ref name=":6">{{Cite journal|last=Silva|first=Patrícia Rocha|last2=Ferreira|first2=Cristina|last3=Bizarro|first3=Susana|last4=Cerveira|first4=Nuno|last5=Torres|first5=Lurdes|last6=Moreira|first6=Ilídia|last7=Mariz|first7=José Mário|date=2015-06|title=Diagnosis, complications and management of chronic neutrophilic leukaemia: A case report|url=https://pubmed.ncbi.nlm.nih.gov/26137123|journal=Oncology Letters|volume=9|issue=6|pages=2657–2660|doi=10.3892/ol.2015.3148|issn=1792-1074|pmc=4473643|pmid=26137123}}</ref>  However, the disease can affect virtually any tissue type.
==Morphologic Features==
Peripheral Blood: typically persistent leukocytosis >3 months with white blood cells composed predominantly of bands and segmented neutrophils exceeding or equaling 80% of white blood cells.  The neutrophils have frequent Dohle bodies, sometimes vacuolation and hypersegmentation <ref name=":4">{{Cite journal|last=Bj|first=Bain|last2=S|first2=Ahmad|date=2015|title=Chronic neutrophilic leukaemia and plasma cell-related neutrophilic leukaemoid reactions|url=https://pubmed.ncbi.nlm.nih.gov/26218186/|language=en|pmid=26218186}}</ref>. Toxic granulation may be present.  Most CNL patients also have mild anemia and thrombocytopenia <ref name=":1" />
Bone marrow: hypercellularity with elevated myeloid to erythroid ratio (often > 10:1), due to increase in neutrophilic granulocyte proliferation, with normal maturation and minimal to absent dysplastic changes. Ingestion of neutrophils by macrophages can be seen.  Erythroid lineage and megakaryocytes are normal.  Less than 5% of nucleated cells are myeloblasts.<ref>Chronic Neutrophilic Leukemia  in Bone Marrow Pathology. Kathryn Foucar, Kaaren Reichard, David Czuchlewski, ASCP Press, 2020, p284-288.</ref>  The development of dysplastic features may herald disease progression or transformation to acute myeloid leukemia.<ref name=":0" /><ref name=":6" />
==Immunophenotype==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||<span class="blue-text">EXAMPLE:</span> CD1
|-
|Positive (subset)||<span class="blue-text">EXAMPLE:</span> CD2
|-
|Negative (universal)||<span class="blue-text">EXAMPLE:</span> CD3
|-
|Negative (subset)||<span class="blue-text">EXAMPLE:</span> CD4
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Immunophenotype|The content below was from the old template. Please incorporate above.}}</blockquote>
There is no specific immunophenotype.<ref name=":0" />
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
</blockquote>
==WHO Essential and Desirable Genetic Diagnostic Criteria==
==WHO Essential and Desirable Genetic Diagnostic Criteria==
<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>
<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>
Line 211: Line 130:
|}
|}


<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:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}</blockquote>
CNL is by definition Philadelphia chromosome negative (BCR/ABL1-negative).<ref name=":0" />  
CNL is by definition Philadelphia chromosome negative (BCR/ABL1-negative).<ref name=":0">Bain BJ, et al., (2017). Chronic Neutrophilic Leukaemia, 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. IARC Press: Lyon, France, p37-38.</ref>  
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
Line 226: Line 145:




<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
<blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
* Chromosomal Rearrangements (Gene Fusions)
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Individual Region Genomic Gain/Loss/LOH
Line 232: Line 151:
* Gene Mutations (SNV/INDEL)}}</blockquote>
* Gene Mutations (SNV/INDEL)}}</blockquote>


CNL can progress to myeloma or blastic transformation to acute myeloid leukemia.<ref name=":1" />  It can also transform in other forms of MPN (PV or CMML). The presence of ''ASXL1'' as secondary mutation confers worse prognosis.<ref name=":0" /><ref name=":8">{{Cite journal|last=Ma|first=Elliott|last2=A|first2=Pardanani|last3=Ca|first3=Hanson|last4=Tl|first4=Lasho|last5=Cm|first5=Finke|last6=Aa|first6=Belachew|last7=A|first7=Tefferi|date=2015|title=ASXL1 mutations are frequent and prognostically detrimental in CSF3R-mutated chronic neutrophilic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/25850813/|language=en|pmid=25850813}}</ref>
CNL can progress to myeloma or blastic transformation to acute myeloid leukemia.<ref name=":1">{{Cite journal|last=N|first=Szuber|last2=A|first2=Tefferi|date=2018|title=Chronic neutrophilic leukemia: new science and new diagnostic criteria|url=https://pubmed.ncbi.nlm.nih.gov/29440636/|language=en|doi=10.1038/s41408-018-0049-8|pmc=PMC5811432|pmid=29440636}}</ref>  It can also transform in other forms of MPN (PV or CMML). The presence of ''ASXL1'' as secondary mutation confers worse prognosis.<ref name=":0" /><ref name=":8">{{Cite journal|last=Ma|first=Elliott|last2=A|first2=Pardanani|last3=Ca|first3=Hanson|last4=Tl|first4=Lasho|last5=Cm|first5=Finke|last6=Aa|first6=Belachew|last7=A|first7=Tefferi|date=2015|title=ASXL1 mutations are frequent and prognostically detrimental in CSF3R-mutated chronic neutrophilic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/25850813/|language=en|pmid=25850813}}</ref>


Thrombocytopenia also proves to be an adverse prognostic factor. Patients with CNL have a hemorrhagic tendency, leading to cerebral hemorrhage as the most significant registered cause of death.<ref>{{Cite journal|last=T|first=Mitsumori|last2=N|first2=Komatsu|last3=K|first3=Kirito|date=2016|title=A CSF3R T618I Mutation in a Patient with Chronic Neutrophilic Leukemia and Severe Bleeding Complications|url=https://pubmed.ncbi.nlm.nih.gov/26875968/|language=en|pmid=26875968}}</ref>  Other causes of death include generalized leukemic tissue infiltration, ileus caused by a granulocytic and myelocytic infiltration of the small bowel, and pneumonia.<ref name=":2">{{Cite journal|last=J|first=Böhm|last2=He|first2=Schaefer|date=2002|title=Chronic neutrophilic leukaemia: 14 new cases of an uncommon myeloproliferative disease|url=https://pubmed.ncbi.nlm.nih.gov/12401827/|language=en|doi=10.1136/jcp.55.11.862|pmc=PMC1769801|pmid=12401827}}</ref> 
Thrombocytopenia also proves to be an adverse prognostic factor. Patients with CNL have a hemorrhagic tendency, leading to cerebral hemorrhage as the most significant registered cause of death.<ref>{{Cite journal|last=T|first=Mitsumori|last2=N|first2=Komatsu|last3=K|first3=Kirito|date=2016|title=A CSF3R T618I Mutation in a Patient with Chronic Neutrophilic Leukemia and Severe Bleeding Complications|url=https://pubmed.ncbi.nlm.nih.gov/26875968/|language=en|pmid=26875968}}</ref>  Other causes of death include generalized leukemic tissue infiltration, ileus caused by a granulocytic and myelocytic infiltration of the small bowel, and pneumonia.<ref name=":2">{{Cite journal|last=J|first=Böhm|last2=He|first2=Schaefer|date=2002|title=Chronic neutrophilic leukaemia: 14 new cases of an uncommon myeloproliferative disease|url=https://pubmed.ncbi.nlm.nih.gov/12401827/|language=en|doi=10.1136/jcp.55.11.862|pmc=PMC1769801|pmid=12401827}}</ref> 


Treatment: There is currently no standard of care or established guidelines for the management of CNL. As such, treatment may involve several therapeutic approaches.<ref name=":3" />  Blood transfusions when necessary, hydroxyurea, allogeneic bone marrow transplantation. Clinical remission has been achieved in instances with long-term interferon α treatment.<ref name=":2" />  Hydroxyurea is the most used therapy, but often requires a second or third line therapy.<ref name=":3" /><ref name=":5" /><ref name=":6" />  Other potential pharmacologic agents include imatinib, ruxolitinib, interferon-alpha(IFN-α), hypomethylating agents, thalidomide, and cladribine.  These may be used in combination.<ref name=":6" /><ref name=":3" /><ref>{{Cite journal|last=Dao|first=Kim-Hien T.|last2=Gotlib|first2=Jason|last3=Deininger|first3=Michael M. N.|last4=Oh|first4=Stephen T.|last5=Cortes|first5=Jorge E.|last6=Collins|first6=Robert H.|last7=Winton|first7=Elliot F.|last8=Parker|first8=Dana R.|last9=Lee|first9=Hyunjung|date=2020-04-01|title=Efficacy of Ruxolitinib in Patients With Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/31880950|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=38|issue=10|pages=1006–1018|doi=10.1200/JCO.19.00895|issn=1527-7755|pmc=7106977|pmid=31880950}}</ref><ref>{{Cite journal|last=Gunawan|first=Arief S.|last2=McLornan|first2=Donal P.|last3=Wilkins|first3=Bridget|last4=Waghorn|first4=Katherine|last5=Hoade|first5=Yvette|last6=Cross|first6=Nicholas C. P.|last7=Harrison|first7=Claire N.|date=06 2017|title=Ruxolitinib, a potent JAK1/JAK2 inhibitor, induces temporary reductions in the allelic burden of concurrent CSF3R mutations in chronic neutrophilic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/28302714|journal=Haematologica|volume=102|issue=6|pages=e238–e240|doi=10.3324/haematol.2017.163790|issn=1592-8721|pmc=5451352|pmid=28302714}}</ref>  Cases with ''CSF3R'' T618I mutation may respond to treatment with Ruxolitinib (JAK inhibitor) while cases with ''CSF3R'' truncation mutations may be sensitive to Dasatinib (SRC kinase inhibitor).<ref name=":1" />
Treatment: There is currently no standard of care or established guidelines for the management of CNL. As such, treatment may involve several therapeutic approaches.<ref name=":3">{{Cite journal|last=Szuber|first=Natasha|last2=Elliott|first2=Michelle|last3=Tefferi|first3=Ayalew|date=02 2020|title=Chronic neutrophilic leukemia: 2020 update on diagnosis, molecular genetics, prognosis, and management|url=https://pubmed.ncbi.nlm.nih.gov/31769070|journal=American Journal of Hematology|volume=95|issue=2|pages=212–224|doi=10.1002/ajh.25688|issn=1096-8652|pmid=31769070}}</ref>  Blood transfusions when necessary, hydroxyurea, allogeneic bone marrow transplantation. Clinical remission has been achieved in instances with long-term interferon α treatment.<ref name=":2" />  Hydroxyurea is the most used therapy, but often requires a second or third line therapy.<ref name=":3" /><ref name=":5">{{Cite journal|last=Elliott|first=M. A.|last2=Hanson|first2=C. A.|last3=Dewald|first3=G. W.|last4=Smoley|first4=S. A.|last5=Lasho|first5=T. L.|last6=Tefferi|first6=A.|date=2005-02|title=WHO-defined chronic neutrophilic leukemia: a long-term analysis of 12 cases and a critical review of the literature|url=https://pubmed.ncbi.nlm.nih.gov/15549147|journal=Leukemia|volume=19|issue=2|pages=313–317|doi=10.1038/sj.leu.2403562|issn=0887-6924|pmid=15549147}}</ref><ref name=":6">{{Cite journal|last=Silva|first=Patrícia Rocha|last2=Ferreira|first2=Cristina|last3=Bizarro|first3=Susana|last4=Cerveira|first4=Nuno|last5=Torres|first5=Lurdes|last6=Moreira|first6=Ilídia|last7=Mariz|first7=José Mário|date=2015-06|title=Diagnosis, complications and management of chronic neutrophilic leukaemia: A case report|url=https://pubmed.ncbi.nlm.nih.gov/26137123|journal=Oncology Letters|volume=9|issue=6|pages=2657–2660|doi=10.3892/ol.2015.3148|issn=1792-1074|pmc=4473643|pmid=26137123}}</ref>  Other potential pharmacologic agents include imatinib, ruxolitinib, interferon-alpha(IFN-α), hypomethylating agents, thalidomide, and cladribine.  These may be used in combination.<ref name=":6" /><ref name=":3" /><ref>{{Cite journal|last=Dao|first=Kim-Hien T.|last2=Gotlib|first2=Jason|last3=Deininger|first3=Michael M. N.|last4=Oh|first4=Stephen T.|last5=Cortes|first5=Jorge E.|last6=Collins|first6=Robert H.|last7=Winton|first7=Elliot F.|last8=Parker|first8=Dana R.|last9=Lee|first9=Hyunjung|date=2020-04-01|title=Efficacy of Ruxolitinib in Patients With Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/31880950|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=38|issue=10|pages=1006–1018|doi=10.1200/JCO.19.00895|issn=1527-7755|pmc=7106977|pmid=31880950}}</ref><ref>{{Cite journal|last=Gunawan|first=Arief S.|last2=McLornan|first2=Donal P.|last3=Wilkins|first3=Bridget|last4=Waghorn|first4=Katherine|last5=Hoade|first5=Yvette|last6=Cross|first6=Nicholas C. P.|last7=Harrison|first7=Claire N.|date=06 2017|title=Ruxolitinib, a potent JAK1/JAK2 inhibitor, induces temporary reductions in the allelic burden of concurrent CSF3R mutations in chronic neutrophilic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/28302714|journal=Haematologica|volume=102|issue=6|pages=e238–e240|doi=10.3324/haematol.2017.163790|issn=1592-8721|pmc=5451352|pmid=28302714}}</ref>  Cases with ''CSF3R'' T618I mutation may respond to treatment with Ruxolitinib (JAK inhibitor) while cases with ''CSF3R'' truncation mutations may be sensitive to Dasatinib (SRC kinase inhibitor).<ref name=":1" />


The presenting features may be non-specific with organomegaly involving the liver, spleen or both, mucocutaneous bleeding, and bruising.<ref name=":0" />  The disease has a variable prognosis with some cases rapidly evolving<ref name=":6" /><ref>{{Cite journal|last=Zittoun|first=R.|last2=Réa|first2=D.|last3=Ngoc|first3=L. H.|last4=Ramond|first4=S.|date=1994-02|title=Chronic neutrophilic leukemia. A study of four cases|url=https://pubmed.ncbi.nlm.nih.gov/8148416|journal=Annals of Hematology|volume=68|issue=2|pages=55–60|doi=10.1007/BF01715131|issn=0939-5555|pmid=8148416}}</ref>; others may have an indolent course spanning decades.<ref>{{Cite journal|last=Uppal|first=Guldeep|last2=Gong|first2=Jerald|date=2015-09|title=Chronic neutrophilic leukaemia|url=https://pubmed.ncbi.nlm.nih.gov/26082513|journal=Journal of Clinical Pathology|volume=68|issue=9|pages=680–684|doi=10.1136/jclinpath-2015-203060|issn=1472-4146|pmid=26082513}}</ref>  Survival is variable, overall mean survival being between 21-30 months.
The presenting features may be non-specific with organomegaly involving the liver, spleen or both, mucocutaneous bleeding, and bruising.<ref name=":0" />  The disease has a variable prognosis with some cases rapidly evolving<ref name=":6" /><ref>{{Cite journal|last=Zittoun|first=R.|last2=Réa|first2=D.|last3=Ngoc|first3=L. H.|last4=Ramond|first4=S.|date=1994-02|title=Chronic neutrophilic leukemia. A study of four cases|url=https://pubmed.ncbi.nlm.nih.gov/8148416|journal=Annals of Hematology|volume=68|issue=2|pages=55–60|doi=10.1007/BF01715131|issn=0939-5555|pmid=8148416}}</ref>; others may have an indolent course spanning decades.<ref>{{Cite journal|last=Uppal|first=Guldeep|last2=Gong|first2=Jerald|date=2015-09|title=Chronic neutrophilic leukaemia|url=https://pubmed.ncbi.nlm.nih.gov/26082513|journal=Journal of Clinical Pathology|volume=68|issue=9|pages=680–684|doi=10.1136/jclinpath-2015-203060|issn=1472-4146|pmid=26082513}}</ref>  Survival is variable, overall mean survival being between 21-30 months.
Line 336: Line 255:
|}
|}


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


Karyotypic abnormalities occur in ~10% of cases while 90% of CNL cases demonstrate a normal karyotype.<ref name=":0" /><ref name=":1" />  There are no diagnostic gains, chromosome losses or losses of heterozygosity (LOH) associated with CNL.   
Karyotypic abnormalities occur in ~10% of cases while 90% of CNL cases demonstrate a normal karyotype.<ref name=":0" /><ref name=":1" />  There are no diagnostic gains, chromosome losses or losses of heterozygosity (LOH) associated with CNL.   
Line 398: Line 317:
|}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.
|}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.


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


CNL has been strongly associated with mutations in ''CSF3R''.<ref name=":3" /><ref name=":7" />  Two types of ''CSF3R'' mutations have been described.  The first is a missense mutation involving the juxta-membrane region (e.g. T618I, the most common ''CSF3R'' mutation in CNL).  The other results in a nonsense or frameshift mutation leading to a truncated protein and subsequent loss of the C-terminus tail region (e.g. ''CSF3R'' D771fs, S783 fs, Y752X, and W791Z).<ref name=":3" /><ref name=":7" />   CNL can also be associated with several genes involved in mRNA splicing, epigenetic modifications, and signaling proteins.   Notably, mutations in ''SETBP1'' and ''ASXL1'' have been described as frequent co-occurrences in association with mutated ''CSF3R''.<ref name=":7" /><ref name=":8" />  Less frequently, concurrent ''JAK2'' mutations have also been identified with mutated ''CSF3R''.<ref name=":0" /><ref name=":3" /><ref name=":7" /><ref name=":8" />
CNL has been strongly associated with mutations in ''CSF3R''.<ref name=":3" /><ref name=":7" />  Two types of ''CSF3R'' mutations have been described.  The first is a missense mutation involving the juxta-membrane region (e.g. T618I, the most common ''CSF3R'' mutation in CNL).  The other results in a nonsense or frameshift mutation leading to a truncated protein and subsequent loss of the C-terminus tail region (e.g. ''CSF3R'' D771fs, S783 fs, Y752X, and W791Z).<ref name=":3" /><ref name=":7" />   CNL can also be associated with several genes involved in mRNA splicing, epigenetic modifications, and signaling proteins.   Notably, mutations in ''SETBP1'' and ''ASXL1'' have been described as frequent co-occurrences in association with mutated ''CSF3R''.<ref name=":7" /><ref name=":8" />  Less frequently, concurrent ''JAK2'' mutations have also been identified with mutated ''CSF3R''.<ref name=":0" /><ref name=":3" /><ref name=":7" /><ref name=":8" />
Line 461: Line 380:
|}
|}


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


Colony-stimulating factor 3 receptor (''CSF3R'') is a gene located on chromosome 1p34.3 encoding the cytokine receptor for granulocyte colony-stimulating factor (G-CSF) or otherwise known as colony-stimulating factor 3 (CSF 3). Its binding activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT), Ras/Raf/MAP kinases, and PI3K/Akt pathways; ''CSF3R'' has been shown to signal through the JAK–STAT pathway, the nonreceptor tyrosine kinase ''SYK'', and the SRC family kinase ''LYN''.<ref>{{Cite journal|last=Corey|first=S. J.|last2=Dombrosky-Ferlan|first2=P. M.|last3=Zuo|first3=S.|last4=Krohn|first4=E.|last5=Donnenberg|first5=A. D.|last6=Zorich|first6=P.|last7=Romero|first7=G.|last8=Takata|first8=M.|last9=Kurosaki|first9=T.|date=1998-02-06|title=Requirement of Src kinase Lyn for induction of DNA synthesis by granulocyte colony-stimulating factor|url=https://pubmed.ncbi.nlm.nih.gov/9452436|journal=The Journal of Biological Chemistry|volume=273|issue=6|pages=3230–3235|doi=10.1074/jbc.273.6.3230|issn=0021-9258|pmid=9452436}}</ref><ref>{{Cite journal|last=Corey|first=S. J.|last2=Burkhardt|first2=A. L.|last3=Bolen|first3=J. B.|last4=Geahlen|first4=R. L.|last5=Tkatch|first5=L. S.|last6=Tweardy|first6=D. J.|date=1994-05-24|title=Granulocyte colony-stimulating factor receptor signaling involves the formation of a three-component complex with Lyn and Syk protein-tyrosine kinases|url=https://pubmed.ncbi.nlm.nih.gov/8197119|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=91|issue=11|pages=4683–4687|doi=10.1073/pnas.91.11.4683|issn=0027-8424|pmc=PMC43852|pmid=8197119}}</ref>  In bone marrow it stimulates granulopoesis by inducing proliferation and differentiation of precursor cells into mature granulocytes.<ref name=":1" />
Colony-stimulating factor 3 receptor (''CSF3R'') is a gene located on chromosome 1p34.3 encoding the cytokine receptor for granulocyte colony-stimulating factor (G-CSF) or otherwise known as colony-stimulating factor 3 (CSF 3). Its binding activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT), Ras/Raf/MAP kinases, and PI3K/Akt pathways; ''CSF3R'' has been shown to signal through the JAK–STAT pathway, the nonreceptor tyrosine kinase ''SYK'', and the SRC family kinase ''LYN''.<ref>{{Cite journal|last=Corey|first=S. J.|last2=Dombrosky-Ferlan|first2=P. M.|last3=Zuo|first3=S.|last4=Krohn|first4=E.|last5=Donnenberg|first5=A. D.|last6=Zorich|first6=P.|last7=Romero|first7=G.|last8=Takata|first8=M.|last9=Kurosaki|first9=T.|date=1998-02-06|title=Requirement of Src kinase Lyn for induction of DNA synthesis by granulocyte colony-stimulating factor|url=https://pubmed.ncbi.nlm.nih.gov/9452436|journal=The Journal of Biological Chemistry|volume=273|issue=6|pages=3230–3235|doi=10.1074/jbc.273.6.3230|issn=0021-9258|pmid=9452436}}</ref><ref>{{Cite journal|last=Corey|first=S. J.|last2=Burkhardt|first2=A. L.|last3=Bolen|first3=J. B.|last4=Geahlen|first4=R. L.|last5=Tkatch|first5=L. S.|last6=Tweardy|first6=D. J.|date=1994-05-24|title=Granulocyte colony-stimulating factor receptor signaling involves the formation of a three-component complex with Lyn and Syk protein-tyrosine kinases|url=https://pubmed.ncbi.nlm.nih.gov/8197119|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=91|issue=11|pages=4683–4687|doi=10.1073/pnas.91.11.4683|issn=0027-8424|pmc=PMC43852|pmid=8197119}}</ref>  In bone marrow it stimulates granulopoesis by inducing proliferation and differentiation of precursor cells into mature granulocytes.<ref name=":1" />
Line 487: Line 406:
(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 />
(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 />


'''
<br />


==Notes==
==Notes==
Line 496: Line 415:
          
          
<nowiki>*</nowiki>''Citation of this Page'': “Chronic neutrophilic leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Chronic_neutrophilic_leukaemia</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “Chronic neutrophilic leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Chronic_neutrophilic_leukaemia</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases C]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:Diseases C]]
Retrieved from "https://test.ccga.io/index.php/HAEM5:Chronic_neutrophilic_leukaemia"