HAEM5:Chronic myelomonocytic leukaemia: Difference between revisions

The clinical features are variable and significantly related to blood cell counts<ref name=":1" /><ref name=":2">Arber DA, et al., (2017). Introduction and overview of the classification of myeloid neoplasms, 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, Editors. IARC Press: Lyon, France, p82-86.</ref>. Some clinical presentations may be different in dysplastic (WBC count < 13 x 10⁹/L) and proliferative (WBC count ≥ 13 x 10⁹/L) subgroups<ref name=":0" />. In patients with increased white blood cell (WBC) count (~50% of all cases), constitutional symptoms (e.g. weight loss, fever, and night sweats) are common. In cases with cytopenia(s), similar to [[HAEM4:Myelodysplastic Syndromes (MDS)|MDS]], clinical presentations are usually related to insufficient blood cells (anemia, leukopenia and/or thrombocytopenia, e.g. fatigue, infection, and bleeding tendency)<ref>Storniolo AM, Moloney WC, Rosenthal DS, Cox C, Bennett JM. Chronic myelomonocytic leukemia. ''Leukemia''. 1990;4(11):766‐770.</ref>. Hepatosplenomegaly can be present in both subgroups, but are frequently related to leukocytosis. Rare cases with life-threatening hyperleukocytosis have been reported.  

</blockquote>

==Sites of Involvement==

No chromosome rearrangements  specifically associated with CMML.

By definition, the presence of ''BCR-ABL1''1 or rearrangements involving ''PDGFRA, PDGFRB'' or ''FGFR1'' and ''PCM1-JAK2'' defines categories other than CMML.

</blockquote>

* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

Presence of  one or more mutations, especially concurrent mutations in ''TET2'' and ''SRSF2'' is very helpful for a definitive diagnosis.

Somatic ''ASXL1'' mutation has also been incorporated in a clinical prognostic scoring system<ref name=":6" />.

</blockquote>

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

|}

Clonal cytogenetic abnormalities are found in 20-40% of CMML cases, but there are no specific abnormalities<ref>{{Cite journal|last=Such|first=E.|last2=Cervera|first2=J.|last3=Costa|first3=D.|last4=Sole|first4=F.|last5=Vallespi|first5=T.|last6=Luno|first6=E.|last7=Collado|first7=R.|last8=Calasanz|first8=M. J.|last9=Hernandez-Rivas|first9=J. M.|date=2011|title=Cytogenetic risk stratification in chronic myelomonocytic leukemia|url=http://www.haematologica.org/cgi/doi/10.3324/haematol.2010.030957|journal=Haematologica|language=en|volume=96|issue=3|pages=375–383|doi=10.3324/haematol.2010.030957|issn=0390-6078|pmc=PMC3046268|pmid=21109693}}</ref>.

|}

</blockquote>

==Characteristic Chromosomal Patterns==

|}

No characteristic chromosome aberrations identified in association with CMML.

</blockquote>

==Gene Mutations (SNV / INDEL)==

Over 90% of CMML patients studied exhibited one or more mutations<ref name=":2" />. Concurrent mutations in ''TET2'' and ''SRSF2'' appear to be highly specific for this entity<ref name=":3">{{Cite journal|last=Ti|first=Mughal|last2=Nc|first2=Cross|last3=E|first3=Padron|last4=Rv|first4=Tiu|last5=M|first5=Savona|last6=L|first6=Malcovati|last7=R|first7=Tibes|last8=Rs|first8=Komrokji|last9=Jj|first9=Kiladjian|date=2015|title=An International MDS/MPN Working Group's Perspective and Recommendations on Molecular Pathogenesis, Diagnosis and Clinical Characterization of Myelodysplastic/Myeloproliferative Neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/26341525/|language=en|doi=10.3324/haematol.2014.114660|pmc=PMC4800699|pmid=26341525}}</ref><ref>{{Cite journal|last=Gelsi-Boyer|first=Véronique|last2=Trouplin|first2=Virginie|last3=Adélaïde|first3=José|last4=Aceto|first4=Nicola|last5=Remy|first5=Virginie|last6=Pinson|first6=Stephane|last7=Houdayer|first7=Claude|last8=Arnoulet|first8=Christine|last9=Sainty|first9=Danielle|date=2008|title=Genome profiling of chronic myelomonocytic leukemia: frequent alterations of RAS and RUNX1genes|url=http://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-8-299|journal=BMC Cancer|language=en|volume=8|issue=1|doi=10.1186/1471-2407-8-299|issn=1471-2407|pmc=PMC2588460|pmid=18925961}}</ref>. Mutations in certain pathways correlated with clinical classification (dysplastic vs. proliferative)<ref name=":7">{{Cite journal|last=Patel|first=B J|last2=Przychodzen|first2=B|last3=Thota|first3=S|last4=Radivoyevitch|first4=T|last5=Visconte|first5=V|last6=Kuzmanovic|first6=T|last7=Clemente|first7=M|last8=Hirsch|first8=C|last9=Morawski|first9=A|date=2017|title=Genomic determinants of chronic myelomonocytic leukemia|url=http://www.nature.com/articles/leu2017164|journal=Leukemia|language=en|volume=31|issue=12|pages=2815–2823|doi=10.1038/leu.2017.164|issn=0887-6924}}</ref>.

The clonal evolution and secondary subclonal hierarchy may be correlated with clinical phenotypes or outcomes<ref name=":7" />.

</blockquote>

==Epigenomic Alterations==