Difference between revisions of "HAEM5:Chronic neutrophilic leukaemia"
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{{DISPLAYTITLE:Chronic neutrophilic leukaemia}} | {{DISPLAYTITLE:Chronic neutrophilic leukaemia}} | ||
| − | [[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]] | + | [[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]] |
{{Under Construction}} | {{Under Construction}} | ||
| − | <blockquote class='blockedit'>{{Box-round|title= | + | <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> | ||
| − | <span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples). Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span> | + | <span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span> |
==Primary Author(s)*== | ==Primary Author(s)*== | ||
| Line 46: | Line 46: | ||
==Clinical Features== | ==Clinical Features== | ||
| − | Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span> | + | 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" | {| class="wikitable" | ||
|'''Signs and Symptoms''' | |'''Signs and Symptoms''' | ||
| − | |EXAMPLE Asymptomatic (incidental finding on complete blood counts) | + | |<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts) |
| − | EXAMPLE B-symptoms (weight loss, fever, night sweats) | + | <span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats) |
| − | EXAMPLE Fatigue | + | <span class="blue-text">EXAMPLE:</span> Fatigue |
| − | EXAMPLE Lymphadenopathy (uncommon) | + | <span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon) |
|- | |- | ||
|'''Laboratory Findings''' | |'''Laboratory Findings''' | ||
| − | |EXAMPLE Cytopenias | + | |<span class="blue-text">EXAMPLE:</span> Cytopenias |
| − | EXAMPLE Lymphocytosis (low level) | + | <span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level) |
|} | |} | ||
| Line 82: | Line 82: | ||
==Immunophenotype== | ==Immunophenotype== | ||
| − | Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span> | + | 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" | {| class="wikitable sortable" | ||
| Line 88: | Line 88: | ||
!Finding!!Marker | !Finding!!Marker | ||
|- | |- | ||
| − | |Positive (universal)||EXAMPLE CD1 | + | |Positive (universal)||<span class="blue-text">EXAMPLE:</span> CD1 |
|- | |- | ||
| − | |Positive (subset)||EXAMPLE CD2 | + | |Positive (subset)||<span class="blue-text">EXAMPLE:</span> CD2 |
|- | |- | ||
| − | |Negative (universal)||EXAMPLE CD3 | + | |Negative (universal)||<span class="blue-text">EXAMPLE:</span> CD3 |
|- | |- | ||
| − | |Negative (subset)||EXAMPLE CD4 | + | |Negative (subset)||<span class="blue-text">EXAMPLE:</span> CD4 |
|} | |} | ||
| Line 115: | Line 115: | ||
!Notes | !Notes | ||
|- | |- | ||
| − | |EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC) | + | |<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)||<span class="blue-text">EXAMPLE:</span> 3'ABL1 / 5'BCR||<span class="blue-text">EXAMPLE:</span> der(22)||<span class="blue-text">EXAMPLE:</span> 20% (COSMIC) |
| − | EXAMPLE 30% (add reference) | + | <span class="blue-text">EXAMPLE:</span> 30% (add reference) |
|Yes | |Yes | ||
|No | |No | ||
|Yes | |Yes | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). | The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). | ||
| Line 154: | Line 154: | ||
==Individual Region Genomic Gain / Loss / LOH== | ==Individual Region Genomic Gain / Loss / LOH== | ||
| − | Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span> | + | Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.'') </span> |
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
| Line 164: | Line 164: | ||
!Notes | !Notes | ||
|- | |- | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
7 | 7 | ||
| − | |EXAMPLE Loss | + | |<span class="blue-text">EXAMPLE:</span> Loss |
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
chr7:1- 159,335,973 [hg38] | chr7:1- 159,335,973 [hg38] | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
chr7 | chr7 | ||
| Line 177: | Line 177: | ||
|Yes | |Yes | ||
|No | |No | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference). | Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference). | ||
|- | |- | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
8 | 8 | ||
| − | |EXAMPLE Gain | + | |<span class="blue-text">EXAMPLE:</span> Gain |
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
chr8:1-145,138,636 [hg38] | chr8:1-145,138,636 [hg38] | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
chr8 | chr8 | ||
| Line 194: | Line 194: | ||
|No | |No | ||
|No | |No | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
Common recurrent secondary finding for t(8;21) (add reference). | Common recurrent secondary finding for t(8;21) (add reference). | ||
| Line 200: | Line 200: | ||
==Characteristic Chromosomal Patterns== | ==Characteristic Chromosomal Patterns== | ||
| − | Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span> | + | Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis. Do not delete table.'')</span> |
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
| Line 210: | Line 210: | ||
!Notes | !Notes | ||
|- | |- | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
Co-deletion of 1p and 18q | Co-deletion of 1p and 18q | ||
| Line 216: | Line 216: | ||
|No | |No | ||
|No | |No | ||
| − | |EXAMPLE: | + | |<span class="blue-text">EXAMPLE:</span> |
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). | See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). | ||
| Line 234: | Line 234: | ||
==Gene Mutations (SNV / INDEL)== | ==Gene Mutations (SNV / INDEL)== | ||
| − | Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable | + | Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well as either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable. Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Do not delete table.'') </span> |
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
| Line 244: | Line 244: | ||
!Notes | !Notes | ||
|- | |- | ||
| − | |EXAMPLE: TP53; Variable LOF mutations | + | |<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations |
| − | EXAMPLE: | + | <span class="blue-text">EXAMPLE:</span> |
EGFR; Exon 20 mutations | EGFR; Exon 20 mutations | ||
| − | EXAMPLE: BRAF; Activating mutations | + | <span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations |
| − | |EXAMPLE: TSG | + | |<span class="blue-text">EXAMPLE:</span> TSG |
| − | |EXAMPLE: 20% (COSMIC) | + | |<span class="blue-text">EXAMPLE:</span> 20% (COSMIC) |
| − | EXAMPLE: 30% (add Reference) | + | <span class="blue-text">EXAMPLE:</span> 30% (add Reference) |
| − | |EXAMPLE: IDH1 R123H | + | |<span class="blue-text">EXAMPLE:</span> IDH1 R123H |
| − | |EXAMPLE: EGFR amplification | + | |<span class="blue-text">EXAMPLE:</span> EGFR amplification |
| | | | ||
| | | | ||
| | | | ||
| − | |EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference). | + | |<span class="blue-text">EXAMPLE:</span> Excludes hairy cell leukemia (HCL) (add reference). |
<br /> | <br /> | ||
|} | |} | ||
| Line 303: | Line 303: | ||
==Genes and Main Pathways Involved== | ==Genes and Main Pathways Involved== | ||
| − | Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span> | + | Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table. Do not delete table.'')</span> |
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
|- | |- | ||
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome | !Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome | ||
|- | |- | ||
| − | |EXAMPLE: BRAF and MAP2K1; Activating mutations | + | |<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations |
| − | |EXAMPLE: MAPK signaling | + | |<span class="blue-text">EXAMPLE:</span> MAPK signaling |
| − | |EXAMPLE: Increased cell growth and proliferation | + | |<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation |
|- | |- | ||
| − | |EXAMPLE: CDKN2A; Inactivating mutations | + | |<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations |
| − | |EXAMPLE: Cell cycle regulation | + | |<span class="blue-text">EXAMPLE:</span> Cell cycle regulation |
| − | |EXAMPLE: Unregulated cell division | + | |<span class="blue-text">EXAMPLE:</span> Unregulated cell division |
|- | |- | ||
| − | |EXAMPLE: KMT2C and ARID1A; Inactivating mutations | + | |<span class="blue-text">EXAMPLE:</span> KMT2C and ARID1A; Inactivating mutations |
| − | |EXAMPLE: Histone modification, chromatin remodeling | + | |<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling |
| − | |EXAMPLE: Abnormal gene expression program | + | |<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program |
|} | |} | ||
Revision as of 16:54, 6 September 2024
Haematolymphoid Tumours (WHO Classification, 5th ed.)
 | This page is under construction |
editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition ClassificationThis page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Chronic Neutrophilic Leukemia (CNL).
(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)
Primary Author(s)*
Anamaria Munteanu, MD, Ph.D**, Harbor-UCLA Medical Center, Joseph J. Merlo Jr, MD. Ph.D**, Ashion Analytics, Fabiola Quintero-Rivera, University of California Irvine
**contributed equally
Cancer Category / Type
Cancer Sub-Classification / Subtype
Chronic neutrophilic leukemia
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 x109/L.[1] 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 (BCR-ABL1- positive Chronic Myeloid Leukemia, Polycythemia Vera, Essential Thrombocythemia and Primary Myelofibrosis) and and myelodysplastic syndrome/myeloproliferative neoplasms.[1][2][3] 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.[1]
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[1][4] 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.[3][5]
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 (Instruction: Can include references in the table. Do not delete table.)
| Signs and Symptoms | EXAMPLE: Asymptomatic (incidental finding on complete blood counts)
EXAMPLE: B-symptoms (weight loss, fever, night sweats) EXAMPLE: Fatigue EXAMPLE: Lymphadenopathy (uncommon) |
| Laboratory Findings | EXAMPLE: Cytopenias
EXAMPLE: Lymphocytosis (low level) |
editv4:Clinical FeaturesThe content below was from the old template. Please incorporate above.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.
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.[1][2][6] 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 [3]. Toxic granulation may be present. Most CNL patients also have mild anemia and thrombocytopenia [4]
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.[7] The development of dysplastic features may herald disease progression or transformation to acute myeloid leukemia.[1][6]
Immunophenotype
Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete table.)
| Finding | Marker |
|---|---|
| Positive (universal) | EXAMPLE: CD1 |
| Positive (subset) | EXAMPLE: CD2 |
| Negative (universal) | EXAMPLE: CD3 |
| Negative (subset) | EXAMPLE: CD4 |
editv4:ImmunophenotypeThe content below was from the old template. Please incorporate above.There is no specific immunophenotype.[1]
Chromosomal Rearrangements (Gene Fusions)
Put your text here and fill in the table
| Chromosomal Rearrangement | Genes in Fusion (5’ or 3’ Segments) | Pathogenic Derivative | Prevalence | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|---|---|---|
| EXAMPLE: t(9;22)(q34;q11.2) | EXAMPLE: 3'ABL1 / 5'BCR | EXAMPLE: der(22) | EXAMPLE: 20% (COSMIC)
EXAMPLE: 30% (add reference) |
Yes | No | Yes | EXAMPLE:
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). |
editv4:Chromosomal Rearrangements (Gene Fusions)The content below was from the old template. Please incorporate above.CNL is by definition Philadelphia chromosome negative (BCR/ABL1-negative).[1]
Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence t(15;19)(q13;q13.3) rare
editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).Please incorporate this section into the relevant tables found in:
- Chromosomal Rearrangements (Gene Fusions)
- Individual Region Genomic Gain/Loss/LOH
- Characteristic Chromosomal Patterns
- Gene Mutations (SNV/INDEL)
CNL can progress to myeloma or blastic transformation to acute myeloid leukemia.[4] It can also transform in other forms of MPN (PV or CMML). The presence of ASXL1 as secondary mutation confers worse prognosis.[1][8]
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.[9] Other causes of death include generalized leukemic tissue infiltration, ileus caused by a granulocytic and myelocytic infiltration of the small bowel, and pneumonia.[10]
Treatment: There is currently no standard of care or established guidelines for the management of CNL. As such, treatment may involve several therapeutic approaches.[2] Blood transfusions when necessary, hydroxyurea, allogeneic bone marrow transplantation. Clinical remission has been achieved in instances with long-term interferon α treatment.[10] Hydroxyurea is the most used therapy, but often requires a second or third line therapy.[2][5][6] Other potential pharmacologic agents include imatinib, ruxolitinib, interferon-alpha(IFN-α), hypomethylating agents, thalidomide, and cladribine. These may be used in combination.[6][2][11][12] 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).[4]
The presenting features may be non-specific with organomegaly involving the liver, spleen or both, mucocutaneous bleeding, and bruising.[1] The disease has a variable prognosis with some cases rapidly evolving[6][13]; others may have an indolent course spanning decades.[14] Survival is variable, overall mean survival being between 21-30 months.
Individual Region Genomic Gain / Loss / LOH
Put your text here and fill in the table (Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.)
| Chr # | Gain / Loss / Amp / LOH | Minimal Region Genomic Coordinates [Genome Build] | Minimal Region Cytoband | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|---|---|---|
| EXAMPLE:
7 |
EXAMPLE: Loss | EXAMPLE:
chr7:1- 159,335,973 [hg38] |
EXAMPLE:
chr7 |
Yes | Yes | No | EXAMPLE:
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference). |
| EXAMPLE:
8 |
EXAMPLE: Gain | EXAMPLE:
chr8:1-145,138,636 [hg38] |
EXAMPLE:
chr8 |
No | No | No | EXAMPLE:
Common recurrent secondary finding for t(8;21) (add reference). |
Characteristic Chromosomal Patterns
Put your text here (EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis. Do not delete table.)
| Chromosomal Pattern | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|
| EXAMPLE:
Co-deletion of 1p and 18q |
Yes | No | No | EXAMPLE:
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). |
editv4:Characteristic Chromosomal Aberrations / PatternsThe content below was from the old template. Please incorporate above.Karyotypic abnormalities occur in ~10% of cases while 90% of CNL cases demonstrate a normal karyotype.[1][4] There are no diagnostic gains, chromosome losses or losses of heterozygosity (LOH) associated with CNL.
Non-specific gains of 8 (most frequent), 9, and 21.
Losses have been reported including del(7q), del(20q) (most frequent), del(11q) or 12p.
Sometimes a complex karyotype is present.
Gene Mutations (SNV / INDEL)
Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well as either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable. Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Do not delete table.)
| Gene; Genetic Alteration | Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other) | Prevalence (COSMIC / TCGA / Other) | Concomitant Mutations | Mutually Exclusive Mutations | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|---|---|---|---|
| EXAMPLE: TP53; Variable LOF mutations
EXAMPLE: EGFR; Exon 20 mutations EXAMPLE: BRAF; Activating mutations |
EXAMPLE: TSG | EXAMPLE: 20% (COSMIC)
EXAMPLE: 30% (add Reference) |
EXAMPLE: IDH1 R123H | EXAMPLE: EGFR amplification | EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference).
|
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.
editv4:Gene Mutations (SNV/INDEL)The content below was from the old template. Please incorporate above.CNL has been strongly associated with mutations in CSF3R.[2][15] 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).[2][15] 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.[15][8] Less frequently, concurrent JAK2 mutations have also been identified with mutated CSF3R.[1][2][15][8]
Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other) CSF3R T618I, T615A, truncation[15]
JAK2 V617F Other Mutations
SETBP1, ASXL1, TET2, SRSF2, U2AF1, CALR
Type Gene/Region/Other Concomitant Mutations CSF3R and SETBP1, CSF3R AND ASXL1 Mutually Exclusive JAK2 V617F and CSF3R T618I
Epigenomic Alterations
Put your text here
Genes and Main Pathways Involved
Put your text here and fill in the table (Instructions: Can include references in the table. Do not delete table.)
| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| EXAMPLE: BRAF and MAP2K1; Activating mutations | EXAMPLE: MAPK signaling | EXAMPLE: Increased cell growth and proliferation |
| EXAMPLE: CDKN2A; Inactivating mutations | EXAMPLE: Cell cycle regulation | EXAMPLE: Unregulated cell division |
| EXAMPLE: KMT2C and ARID1A; Inactivating mutations | EXAMPLE: Histone modification, chromatin remodeling | EXAMPLE: Abnormal gene expression program |
editv4:Genes and Main Pathways InvolvedThe content below was from the old template. Please incorporate above.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.[16][17] In bone marrow it stimulates granulopoesis by inducing proliferation and differentiation of precursor cells into mature granulocytes.[4]
Genetic Diagnostic Testing Methods
Gene sequencing, karyotype, peripheral blood smear, flow cytometry, bone marrow biopsy, FISH, NGS.[1]
Familial Forms
No familial forms have been described.
Additional Information
Put your text here
Links
SEER Hematopoietic and Lymphoid Neoplasm Database; Chronic Neutrophilic Leukemia
References
(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted. 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.)
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 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.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Szuber, Natasha; et al. (02 2020). "Chronic neutrophilic leukemia: 2020 update on diagnosis, molecular genetics, prognosis, and management". American Journal of Hematology. 95 (2): 212–224. doi:10.1002/ajh.25688. ISSN 1096-8652. PMID 31769070. Check date values in:
|date=(help) - ↑ 3.0 3.1 3.2 Bj, Bain; et al. (2015). "Chronic neutrophilic leukaemia and plasma cell-related neutrophilic leukaemoid reactions". PMID 26218186.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 N, Szuber; et al. (2018). "Chronic neutrophilic leukemia: new science and new diagnostic criteria". doi:10.1038/s41408-018-0049-8. PMC 5811432. PMID 29440636.CS1 maint: PMC format (link)
- ↑ 5.0 5.1 Elliott, M. A.; et al. (2005-02). "WHO-defined chronic neutrophilic leukemia: a long-term analysis of 12 cases and a critical review of the literature". Leukemia. 19 (2): 313–317. doi:10.1038/sj.leu.2403562. ISSN 0887-6924. PMID 15549147. Check date values in:
|date=(help) - ↑ 6.0 6.1 6.2 6.3 6.4 Silva, Patrícia Rocha; et al. (2015-06). "Diagnosis, complications and management of chronic neutrophilic leukaemia: A case report". Oncology Letters. 9 (6): 2657–2660. doi:10.3892/ol.2015.3148. ISSN 1792-1074. PMC 4473643. PMID 26137123. Check date values in:
|date=(help) - ↑ Chronic Neutrophilic Leukemia in Bone Marrow Pathology. Kathryn Foucar, Kaaren Reichard, David Czuchlewski, ASCP Press, 2020, p284-288.
- ↑ 8.0 8.1 8.2 Ma, Elliott; et al. (2015). "ASXL1 mutations are frequent and prognostically detrimental in CSF3R-mutated chronic neutrophilic leukemia". PMID 25850813.
- ↑ T, Mitsumori; et al. (2016). "A CSF3R T618I Mutation in a Patient with Chronic Neutrophilic Leukemia and Severe Bleeding Complications". PMID 26875968.
- ↑ 10.0 10.1 J, Böhm; et al. (2002). "Chronic neutrophilic leukaemia: 14 new cases of an uncommon myeloproliferative disease". doi:10.1136/jcp.55.11.862. PMC 1769801. PMID 12401827.CS1 maint: PMC format (link)
- ↑ Dao, Kim-Hien T.; et al. (2020-04-01). "Efficacy of Ruxolitinib in Patients With Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 38 (10): 1006–1018. doi:10.1200/JCO.19.00895. ISSN 1527-7755. PMC 7106977 Check
|pmc=value (help). PMID 31880950. - ↑ Gunawan, Arief S.; et al. (06 2017). "Ruxolitinib, a potent JAK1/JAK2 inhibitor, induces temporary reductions in the allelic burden of concurrent CSF3R mutations in chronic neutrophilic leukemia". Haematologica. 102 (6): e238–e240. doi:10.3324/haematol.2017.163790. ISSN 1592-8721. PMC 5451352. PMID 28302714. Check date values in:
|date=(help) - ↑ Zittoun, R.; et al. (1994-02). "Chronic neutrophilic leukemia. A study of four cases". Annals of Hematology. 68 (2): 55–60. doi:10.1007/BF01715131. ISSN 0939-5555. PMID 8148416. Check date values in:
|date=(help) - ↑ Uppal, Guldeep; et al. (2015-09). "Chronic neutrophilic leukaemia". Journal of Clinical Pathology. 68 (9): 680–684. doi:10.1136/jclinpath-2015-203060. ISSN 1472-4146. PMID 26082513. Check date values in:
|date=(help) - ↑ 15.0 15.1 15.2 15.3 15.4 Je, Maxson; et al. (2013). "Oncogenic CSF3R mutations in chronic neutrophilic leukemia and atypical CML". doi:10.1056/NEJMoa1214514. PMC 3730275. PMID 23656643.CS1 maint: PMC format (link)
- ↑ Corey, S. J.; et al. (1998-02-06). "Requirement of Src kinase Lyn for induction of DNA synthesis by granulocyte colony-stimulating factor". The Journal of Biological Chemistry. 273 (6): 3230–3235. doi:10.1074/jbc.273.6.3230. ISSN 0021-9258. PMID 9452436.
- ↑ Corey, S. J.; et al. (1994-05-24). "Granulocyte colony-stimulating factor receptor signaling involves the formation of a three-component complex with Lyn and Syk protein-tyrosine kinases". Proceedings of the National Academy of Sciences of the United States of America. 91 (11): 4683–4687. doi:10.1073/pnas.91.11.4683. ISSN 0027-8424. PMC 43852. PMID 8197119.CS1 maint: PMC format (link)
Notes
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