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{{Chronic neutrophilic leukemia}}
{{Chronic neutrophilic leukemia}}


{{CMG}}; {{AE}}{{Homa}}
{{CMG}}; {{AE}} {{Homa}}; {{GRR}} {{Nat}}


==Overview==
==Overview==
[[Laboratory]] findings consistent with the diagnosis of chronic neutrophilic leukemia (CNL) include [[chronic]] [[neutrophilia]]. Mild [[anemia]], [[thrombocytopenia]], elevation of [[lactate dehydrogenase]] and [[vitamin B12]].
A chronic elevated [[concentration]] of [[blood]] mature [[Neutrophil|neutrophils]] is [[diagnostic]] for chronic neutrophilic leukemia (CNL). There are other [[blood]], [[bone marrow]] and [[genetic]] [[test]]<nowiki/>s which help the [[diagnosis]] of CNL.
 


==Laboratory Findings==
==Laboratory Findings==


A chronic elevated concentration of blood mature [[Neutrophil|neutrophils]] is diagnostic for CNL.<ref name="ElliottHanson2004">{{cite journal|last1=Elliott|first1=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|title=WHO-defined chronic neutrophilic leukemia: a long-term analysis of 12 cases and a critical review of the literature|journal=Leukemia|volume=19|issue=2|year=2004|pages=313–317|issn=0887-6924|doi=10.1038/sj.leu.2403562}}</ref>
A chronic elevated [[concentration]] of [[blood]] mature [[Neutrophil|neutrophils]] is [[diagnostic]] for CNL.<ref name="ElliottHanson2004">{{cite journal|last1=Elliott|first1=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|title=WHO-defined chronic neutrophilic leukemia: a long-term analysis of 12 cases and a critical review of the literature|journal=Leukemia|volume=19|issue=2|year=2004|pages=313–317|issn=0887-6924|doi=10.1038/sj.leu.2403562}}</ref>
 
Some patients with CNL may have:<ref name="HasleOlesen1996">{{cite journal|last1=Hasle|first1=Henrik|last2=Olesen|first2=Gitte|last3=Kerndrup|first3=GITTE|last4=Philip|first4=Preben|last5=Jacobsen|first5=Niels|title=Chronic neutrophil leukaemia in adolescence and young adulthood|journal=British Journal of Haematology|volume=94|issue=4|year=1996|pages=628–630|issn=0007-1048|doi=10.1046/j.1365-2141.1996.7082329.x}}</ref><ref name="ElliottHanson2004">{{cite journal|last1=Elliott|first1=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|title=WHO-defined chronic neutrophilic leukemia: a long-term analysis of 12 cases and a critical review of the literature|journal=Leukemia|volume=19|issue=2|year=2004|pages=313–317|issn=0887-6924|doi=10.1038/sj.leu.2403562}}</ref><ref name="Elliott2006">{{cite journal|last1=Elliott|first1=Michelle A.|title=Chronic neutrophilic leukemia and chronic myelomonocytic leukemia: WHO defined|journal=Best Practice & Research Clinical Haematology|volume=19|issue=3|year=2006|pages=571–593|issn=15216926|doi=10.1016/j.beha.2005.07.012}}</ref>
*Mild [[anemia]]
*[[Thrombocytopenia]]
*Elevation of [[lactate dehydrogenase]] (LDH)
*Elevation of [[vitamin B12]]


Some [[patients]] with CNL may have:<ref name="ElliottHanson2004">{{cite journal|last1=Elliott|first1=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|title=WHO-defined chronic neutrophilic leukemia: a long-term analysis of 12 cases and a critical review of the literature|journal=Leukemia|volume=19|issue=2|year=2004|pages=313–317|issn=0887-6924|doi=10.1038/sj.leu.2403562}}</ref><ref name="HasleOlesen1996">{{cite journal|last1=Hasle|first1=Henrik|last2=Olesen|first2=Gitte|last3=Kerndrup|first3=GITTE|last4=Philip|first4=Preben|last5=Jacobsen|first5=Niels|title=Chronic neutrophil leukaemia in adolescence and young adulthood|journal=British Journal of Haematology|volume=94|issue=4|year=1996|pages=628–630|issn=0007-1048|doi=10.1046/j.1365-2141.1996.7082329.x}}</ref><ref name="Elliott2006">{{cite journal|last1=Elliott|first1=Michelle A.|title=Chronic neutrophilic leukemia and chronic myelomonocytic leukemia: WHO defined|journal=Best Practice & Research Clinical Haematology|volume=19|issue=3|year=2006|pages=571–593|issn=15216926|doi=10.1016/j.beha.2005.07.012}}</ref><ref name="ArberOrazi2016">{{cite journal|last1=Arber|first1=D. A.|last2=Orazi|first2=A.|last3=Hasserjian|first3=R.|last4=Thiele|first4=J.|last5=Borowitz|first5=M. J.|last6=Le Beau|first6=M. M.|last7=Bloomfield|first7=C. D.|last8=Cazzola|first8=M.|last9=Vardiman|first9=J. W.|title=The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia|journal=Blood|volume=127|issue=20|year=2016|pages=2391–2405|issn=0006-4971|doi=10.1182/blood-2016-03-643544}}</ref><ref name="ElliottPardanani2015">{{cite journal|last1=Elliott|first1=Michelle A.|last2=Pardanani|first2=Animesh|last3=Hanson|first3=Curtis A.|last4=Lasho|first4=Terra L.|last5=Finke|first5=Christy M.|last6=Belachew|first6=Alem A.|last7=Tefferi|first7=Ayalew|title=ASXL1mutations are frequent and prognostically detrimental inCSF3R-mutated chronic neutrophilic leukemia|journal=American Journal of Hematology|volume=90|issue=7|year=2015|pages=653–656|issn=03618609|doi=10.1002/ajh.24031}}</ref><ref>{{Cite journal
| author = [[John T. Reilly]]
| title = Chronic neutrophilic leukaemia: a distinct clinical entity?
| journal = [[British journal of haematology]]
| volume = 116
| issue = 1
| pages = 10–18
| year = 2002
| month = January
| pmid = 11841395
}}</ref><ref name="PiliotisKutas2009">{{cite journal|last1=Piliotis|first1=E.|last2=Kutas|first2=G.|last3=Lipton|first3=J.H.|title=Allogeneic Bone Marrow Transplantation in the Management of Chronic Neutrophilic Leukemia|journal=Leukemia & Lymphoma|volume=43|issue=10|year=2009|pages=2051–2054|issn=1042-8194|doi=10.1080/1042819021000016087}}</ref><ref name="DonatoCroci1986">{{cite journal|last1=Donato|first1=Carlo Di|last2=Croci|first2=Gianfranco|last3=Lazzari|first3=Stefano|last4=Scarduelli|first4=Laura|last5=Vignoli|first5=Roberto|last6=Buia|first6=Marco|last7=Tramaloni|first7=Casimiro|last8=Maccari|first8=Sergio|last9=Plancher|first9=Angelo Cesare|title=Chronic Neutrophilic Leukemia: Description of a New Case with Karyotypic Abnormalities|journal=American Journal of Clinical Pathology|volume=85|issue=3|year=1986|pages=369–371|issn=1943-7722|doi=10.1093/ajcp/85.3.369}}</ref><ref>{{Cite journal
| author = [[Michelle A. Elliott]]
| title = Chronic neutrophilic leukemia: a contemporary review
| journal = [[Current hematology reports]]
| volume = 3
| issue = 3
| pages = 210–217
| year = 2004
| month = May
| pmid = 15087070
}}</ref><ref>{{Cite journal
| author = [[Donald P. Mc Lornan]], [[Melanie J. Percy]], [[Amy V. Jones]], [[Nicholas C. P. Cross]] & [[Mary Frances Mc Mullin]]
| title = Chronic neutrophilic leukemia with an associated V617F JAK2 tyrosine kinase mutation
| journal = [[Haematologica]]
| volume = 90
| issue = 12
| pages = 1696–1697
| year = 2005
| month = December
| pmid = 16330446
}}</ref><ref name="PardananiLasho2013">{{cite journal|last1=Pardanani|first1=A|last2=Lasho|first2=T L|last3=Laborde|first3=R R|last4=Elliott|first4=M|last5=Hanson|first5=C A|last6=Knudson|first6=R A|last7=Ketterling|first7=R P|last8=Maxson|first8=J E|last9=Tyner|first9=J W|last10=Tefferi|first10=A|title=CSF3R T618I is a highly prevalent and specific mutation in chronic neutrophilic leukemia|journal=Leukemia|volume=27|issue=9|year=2013|pages=1870–1873|issn=0887-6924|doi=10.1038/leu.2013.122}}</ref><ref name="MaxsonGotlib2013">{{cite journal|last1=Maxson|first1=Julia E.|last2=Gotlib|first2=Jason|last3=Pollyea|first3=Daniel A.|last4=Fleischman|first4=Angela G.|last5=Agarwal|first5=Anupriya|last6=Eide|first6=Christopher A.|last7=Bottomly|first7=Daniel|last8=Wilmot|first8=Beth|last9=McWeeney|first9=Shannon K.|last10=Tognon|first10=Cristina E.|last11=Pond|first11=J. Blake|last12=Collins|first12=Robert H.|last13=Goueli|first13=Basem|last14=Oh|first14=Stephen T.|last15=Deininger|first15=Michael W.|last16=Chang|first16=Bill H.|last17=Loriaux|first17=Marc M.|last18=Druker|first18=Brian J.|last19=Tyner|first19=Jeffrey W.|title=Oncogenic CSF3R Mutations in Chronic Neutrophilic Leukemia and Atypical CML|journal=New England Journal of Medicine|volume=368|issue=19|year=2013|pages=1781–1790|issn=0028-4793|doi=10.1056/NEJMoa1214514}}</ref><ref name="GotlibMaxson2013">{{cite journal|last1=Gotlib|first1=J.|last2=Maxson|first2=J. E.|last3=George|first3=T. I.|last4=Tyner|first4=J. W.|title=The new genetics of chronic neutrophilic leukemia and atypical CML: implications for diagnosis and treatment|journal=Blood|volume=122|issue=10|year=2013|pages=1707–1711|issn=0006-4971|doi=10.1182/blood-2013-05-500959}}</ref><ref name="MeggendorferHaferlach2014">{{cite journal|last1=Meggendorfer|first1=M.|last2=Haferlach|first2=T.|last3=Alpermann|first3=T.|last4=Jeromin|first4=S.|last5=Haferlach|first5=C.|last6=Kern|first6=W.|last7=Schnittger|first7=S.|title=Specific molecular mutation patterns delineate chronic neutrophilic leukemia, atypical chronic myeloid leukemia, and chronic myelomonocytic leukemia|journal=Haematologica|volume=99|issue=12|year=2014|pages=e244–e246|issn=0390-6078|doi=10.3324/haematol.2014.113159}}</ref><ref name="CuiLi2014">{{cite journal|last1=Cui|first1=Yajuan|last2=Li|first2=Bing|last3=Gale|first3=Robert Peter|last4=Jiang|first4=Qian|last5=Xu|first5=Zefeng|last6=Qin|first6=Tiejun|last7=Zhang|first7=Peihong|last8=Zhang|first8=Yue|last9=Xiao|first9=Zhijian|title=CSF3R, SETBP1 and CALR mutations in chronic neutrophilic leukemia|journal=Journal of Hematology & Oncology|volume=7|issue=1|year=2014|issn=1756-8722|doi=10.1186/s13045-014-0077-1}}</ref><ref name="DaoTyner2015">{{cite journal|last1=Dao|first1=K.-H. T.|last2=Tyner|first2=J. W.|title=What's different about atypical CML and chronic neutrophilic leukemia?|journal=Hematology|volume=2015|issue=1|year=2015|pages=264–271|issn=1520-4391|doi=10.1182/asheducation-2015.1.264}}</ref>
===== '''Blood tests:''' =====
===== '''Blood tests:''' =====
* [[Peripheral blood]] [[White blood cells]] (WBC) ≥25 ×10<sup>9</sup>/L
* [[Peripheral blood]] [[White blood cells]] (WBC) ≥25 ×10<sup>9</sup>/L
Line 22: Line 48:
* [[Myeloblast|Myeloblasts]] rarely observed
* [[Myeloblast|Myeloblasts]] rarely observed
* [[Monocyte]] count <1 ×10<sup>9</sup>/L
* [[Monocyte]] count <1 ×10<sup>9</sup>/L
* No dysgranulopoies.
* Mild [[anemia]]
*[[Leukocytosis]] (median of 100,000/µL) with a [[left shift]]
* [[Thrombocytopenia]]
*[[Thrombocytosis]]
*[[Blast|Blasts]] usually number <2%
*Absolute [[basophilia]] is nearly universal
*Absolute [[eosinophilia]]
*[[Monocytosis]]
*[[Thrombocytosis]]
*[[Thrombocytopenia]] suggests an alternative diagnosis or the presence of advanced stage
*Elevated [[uric acid]]
*Elevated [[histamine]] levels due to [[basophilia]]
 
==== '''Differential blood test:''' ====
* A differential (diff), which is a count of the different types of white blood cells in a peripheral blood sample.
 
==='''Peripheral  blood smear:'''===
*Increase in immature myeloid cells at various stage of maturation (i.e. myelocytes and band cells).
 
===== Bone marrow test: =====
*Increase in immature myeloid cells at various stage of maturation (i.e. myelocytes and band cells).
*Presence of translocation between chromosomes 9 and 22.
*Presence of BCR-ABL transcripts by RT-PCR.


==== Blood chemistry tests: ====
==== Blood chemistry tests: ====
*Increased creatinine in some cases.
*Elevation of [[lactate dehydrogenase]] (LDH).
*Increased liver enzymes in some cases.
 
==== Conventional cytogenetics and karyotyping: ====
* This test looks at chromosomes under a microscope.
* The chromosomes can best be seen when the cell is dividing, so a sample of [[blood]] or [[bone marrow]] must be grown ''in vitro'' so that the cells start to divide.
* The leukemia cells in all [[CML]] patients contain an abnormal [[chromosome]] called the [[Philadelphia (Ph) chromosome]], which looks like a shortened version of chromosome 22.
 
==== Fluorescent in situ hybridization (FISH): ====
* FISH is another way to look at chromosomes and is more precise than conventional cytogenetics because it uses fluorescent dyes that only attach to specific genes or parts of [[chromosomes]].
* In [[CML]], FISH can be used to look for specific pieces of the BCR-ABL [[gene]] on chromosomes.  


==== Polymerase chain reaction (PCR): ====
==== Blood vitamin analysis: ====
* This is a highly sensitive test that can be used to look for the BCR-ABL product in [[leukemia]] cells. PCR is useful for quantitation.
*Elevation of [[vitamin B12]]  
* It can be done on blood or bone marrow samples and can detect very small amounts of BCR-ABL, even when Philadelphia chromosome can not be detected with cytogenetic testing.
* It can be used after treatment to see if copies of the BCR-ABL gene are still present.
* If copies of this gene are found it means that the [[leukemia]] is still present.


==== Genetic tests: ====
* Mutations which may seen:
** [[CSF3R]]
** [[SETBP1]]
** [[ASXL1]]
** TET2
** [[EZH2]]
** KDM6A


* [[Cytogenetic]] abnormalities which may seen:
**[[Trisomy 8]]
**[[Trisomy 21]]
**Deletion 11q
**Deletion 20q6
**Deletion Y
**Trisomy 7
**[[Trisomy 9]]
**Detection of JAK2V617F
==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
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[[Category:Up-To-Date]]
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[[Category:Hematology]]
[[Category:Hematology]]
[[Category:Immunology]]
[[Category:Immunology]]
[[Category:Primary care]]

Latest revision as of 20:57, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2]; Grammar Reviewer: Natalie Harpenau, B.S.[3]

Overview

A chronic elevated concentration of blood mature neutrophils is diagnostic for chronic neutrophilic leukemia (CNL). There are other blood, bone marrow and genetic tests which help the diagnosis of CNL.


Laboratory Findings

A chronic elevated concentration of blood mature neutrophils is diagnostic for CNL.[1]

Some patients with CNL may have:[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]

Blood tests:

Blood chemistry tests:

Blood vitamin analysis:

Genetic tests:

References

  1. ↑ 1.0 1.1 Elliott, M A; Hanson, C A; Dewald, G W; Smoley, S A; Lasho, T L; Tefferi, A (2004). "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.
  2. ↑ Hasle, Henrik; Olesen, Gitte; Kerndrup, GITTE; Philip, Preben; Jacobsen, Niels (1996). "Chronic neutrophil leukaemia in adolescence and young adulthood". British Journal of Haematology. 94 (4): 628–630. doi:10.1046/j.1365-2141.1996.7082329.x. ISSN 0007-1048.
  3. ↑ Elliott, Michelle A. (2006). "Chronic neutrophilic leukemia and chronic myelomonocytic leukemia: WHO defined". Best Practice & Research Clinical Haematology. 19 (3): 571–593. doi:10.1016/j.beha.2005.07.012. ISSN 1521-6926.
  4. ↑ Arber, D. A.; Orazi, A.; Hasserjian, R.; Thiele, J.; Borowitz, M. J.; Le Beau, M. M.; Bloomfield, C. D.; Cazzola, M.; Vardiman, J. W. (2016). "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia". Blood. 127 (20): 2391–2405. doi:10.1182/blood-2016-03-643544. ISSN 0006-4971.
  5. ↑ Elliott, Michelle A.; Pardanani, Animesh; Hanson, Curtis A.; Lasho, Terra L.; Finke, Christy M.; Belachew, Alem A.; Tefferi, Ayalew (2015). "ASXL1mutations are frequent and prognostically detrimental inCSF3R-mutated chronic neutrophilic leukemia". American Journal of Hematology. 90 (7): 653–656. doi:10.1002/ajh.24031. ISSN 0361-8609.
  6. ↑ John T. Reilly (2002). "Chronic neutrophilic leukaemia: a distinct clinical entity?". British journal of haematology. 116 (1): 10–18. PMID 11841395. Unknown parameter |month= ignored (help)
  7. ↑ Piliotis, E.; Kutas, G.; Lipton, J.H. (2009). "Allogeneic Bone Marrow Transplantation in the Management of Chronic Neutrophilic Leukemia". Leukemia & Lymphoma. 43 (10): 2051–2054. doi:10.1080/1042819021000016087. ISSN 1042-8194.
  8. ↑ Donato, Carlo Di; Croci, Gianfranco; Lazzari, Stefano; Scarduelli, Laura; Vignoli, Roberto; Buia, Marco; Tramaloni, Casimiro; Maccari, Sergio; Plancher, Angelo Cesare (1986). "Chronic Neutrophilic Leukemia: Description of a New Case with Karyotypic Abnormalities". American Journal of Clinical Pathology. 85 (3): 369–371. doi:10.1093/ajcp/85.3.369. ISSN 1943-7722.
  9. ↑ Michelle A. Elliott (2004). "Chronic neutrophilic leukemia: a contemporary review". Current hematology reports. 3 (3): 210–217. PMID 15087070. Unknown parameter |month= ignored (help)
  10. ↑ Donald P. Mc Lornan, Melanie J. Percy, Amy V. Jones, Nicholas C. P. Cross & Mary Frances Mc Mullin (2005). "Chronic neutrophilic leukemia with an associated V617F JAK2 tyrosine kinase mutation". Haematologica. 90 (12): 1696–1697. PMID 16330446. Unknown parameter |month= ignored (help)
  11. ↑ Pardanani, A; Lasho, T L; Laborde, R R; Elliott, M; Hanson, C A; Knudson, R A; Ketterling, R P; Maxson, J E; Tyner, J W; Tefferi, A (2013). "CSF3R T618I is a highly prevalent and specific mutation in chronic neutrophilic leukemia". Leukemia. 27 (9): 1870–1873. doi:10.1038/leu.2013.122. ISSN 0887-6924.
  12. ↑ Maxson, Julia E.; Gotlib, Jason; Pollyea, Daniel A.; Fleischman, Angela G.; Agarwal, Anupriya; Eide, Christopher A.; Bottomly, Daniel; Wilmot, Beth; McWeeney, Shannon K.; Tognon, Cristina E.; Pond, J. Blake; Collins, Robert H.; Goueli, Basem; Oh, Stephen T.; Deininger, Michael W.; Chang, Bill H.; Loriaux, Marc M.; Druker, Brian J.; Tyner, Jeffrey W. (2013). "Oncogenic CSF3R Mutations in Chronic Neutrophilic Leukemia and Atypical CML". New England Journal of Medicine. 368 (19): 1781–1790. doi:10.1056/NEJMoa1214514. ISSN 0028-4793.
  13. ↑ Gotlib, J.; Maxson, J. E.; George, T. I.; Tyner, J. W. (2013). "The new genetics of chronic neutrophilic leukemia and atypical CML: implications for diagnosis and treatment". Blood. 122 (10): 1707–1711. doi:10.1182/blood-2013-05-500959. ISSN 0006-4971.
  14. ↑ Meggendorfer, M.; Haferlach, T.; Alpermann, T.; Jeromin, S.; Haferlach, C.; Kern, W.; Schnittger, S. (2014). "Specific molecular mutation patterns delineate chronic neutrophilic leukemia, atypical chronic myeloid leukemia, and chronic myelomonocytic leukemia". Haematologica. 99 (12): e244–e246. doi:10.3324/haematol.2014.113159. ISSN 0390-6078.
  15. ↑ Cui, Yajuan; Li, Bing; Gale, Robert Peter; Jiang, Qian; Xu, Zefeng; Qin, Tiejun; Zhang, Peihong; Zhang, Yue; Xiao, Zhijian (2014). "CSF3R, SETBP1 and CALR mutations in chronic neutrophilic leukemia". Journal of Hematology & Oncology. 7 (1). doi:10.1186/s13045-014-0077-1. ISSN 1756-8722.
  16. ↑ Dao, K.-H. T.; Tyner, J. W. (2015). "What's different about atypical CML and chronic neutrophilic leukemia?". Hematology. 2015 (1): 264–271. doi:10.1182/asheducation-2015.1.264. ISSN 1520-4391.

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