HAEM5:Chronic myelomonocytic leukaemia: Difference between revisions

{{DISPLAYTITLE:Chronic myelomonocytic leukaemia}}

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==Primary Author(s)*==

==Clinical Features==

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|'''Signs and Symptoms'''

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|'''Laboratory Findings'''

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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.  

!Notes

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|Yes

|No

|Yes

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).

No chromosome rearrangements  specifically associated with CMML.

* Chromosomal Rearrangements (Gene Fusions)

* Individual Region Genomic Gain/Loss/LOH

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

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!Notes

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7

chr7:1- 159,335,973 [hg38]

chr7

|Yes

|No

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).

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8

chr8:1-145,138,636 [hg38]

chr8

|No

|No

Common recurrent secondary finding for t(8;21) (add reference).

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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>.

==Characteristic Chromosomal Patterns==

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!Notes

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Co-deletion of 1p and 18q

|No

|No

See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

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No characteristic chromosome aberrations identified in association with CMML.

==Gene Mutations (SNV / INDEL)==

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!Notes

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EGFR; Exon 20 mutations

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<br />

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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>.

==Genes and Main Pathways Involved==

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!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome

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==Genetic Diagnostic Testing Methods==

==Links==

==References==