HAEM5:Chronic myelomonocytic leukaemia: Difference between revisions

[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]

<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-11-03. The original page can be found at [[HAEM4:Chronic Myelomonocytic Leukemia (CMML)]].

 

==Cancer Category/Type==

 

 

==Cancer Sub-Classification / Subtype==

 

[[Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)|Myelodysplastic/Myeloproliferative Neoplasm (MDS/MPN)]]

 

 

Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative neoplasm (MDS/MPN) with persistent monocytosis (absolute monocyte count ≥1 x 10⁹/L and ≥10% of leukocytes are monocytes). When myelodysplasia is absent or minimal, clonal evidence(s) of acquired cytogenetic or molecular genetic change(s) in hematopoietic cells, or unexplained monocytosis persisted for ≥3 months supports the diagnosis of CMML.

 

Before a diagnosis of CMML can be rendered, other well-defined myeloid neoplasms that sometimes present with monocytosis, such as ''BCR-ABL1''-positive chronic myeloid leukemia (especially with p190 fusion) and myeloid/lymphoid neoplasms with rearrangement of ''PDGFRA, PDGFRB'', ''FGFR1'' or ''PCM1-JAK2'' must be ruled out. Dysplastic features are usually seen in at least one myeloid lineage. By definition, the blast percentage must be <20%.

 

'''CMML can be subdivided into three categories based on the percentage of blasts and promonocytes (considered blast equivalent) in the peripheral blood and bone marrow'''<ref name=":2" />''':'''

 

'''CMML-0:''' < 2% blasts in the blood and < 5% in the bone marrow; and no Auer rods.

 

 

 

==Synonyms / Terminology==

 

 

 

Historically CMML was classified as a subtype of MDS. The exact incidence of CMML is difficult to calculate based on the published data. Recent studies reported approximate incidence of 0.4 cases per 100,000 population<ref>{{Cite journal|last=Dinmohamed|first=Avinash G.|last2=van Norden|first2=Yvette|last3=Visser|first3=Otto|last4=Posthuma|first4=Eduardus F.M.|last5=Huijgens|first5=Peter C.|last6=Sonneveld|first6=Pieter|last7=van de Loosdrecht|first7=Arjan A.|last8=Jongen-Lavrencic|first8=Mojca|date=2015|title=The use of medical claims to assess incidence, diagnostic procedures and initial treatment of myelodysplastic syndromes and chronic myelomonocytic leukemia in the Netherlands|url=https://linkinghub.elsevier.com/retrieve/pii/S0145212614003774|journal=Leukemia Research|language=en|volume=39|issue=2|pages=177–182|doi=10.1016/j.leukres.2014.11.025}}</ref>. The median patient age at diagnosis is 65-75 years, with a slight male dominance (male-to female ratio of 1.5-3:1)<ref name=":1">Czader, M and Orazi, A. Chapter 45. Myelodysplastic/Myeloproliferative Neoplasms and Related Diseases. In Orazi A, Foucar K, Knowles DM. eds. Knowles Neoplastic Hematopathology. Riverwoods, IL: Wolters Kluwer Health; 2013:1140-1156.</ref><ref name=":0">{{Cite journal|last=Germing|first=Ulrich|last2=Gattermann|first2=Norbert|last3=Minning|first3=Horst|last4=Heyll|first4=Axel|last5=Aul|first5=Carlo|date=1998|title=Problems in the classification of CMML—dysplastic versus proliferative type|url=https://linkinghub.elsevier.com/retrieve/pii/S0145212697001926|journal=Leukemia Research|language=en|volume=22|issue=10|pages=871–878|doi=10.1016/S0145-2126(97)00192-6}}</ref><ref>{{Cite journal|last=Onida|first=Francesco|last2=Kantarjian|first2=Hagop M.|last3=Smith|first3=Terry L.|last4=Ball|first4=Greg|last5=Keating|first5=Michael J.|last6=Estey|first6=Elihu H.|last7=Glassman|first7=Armand B.|last8=Albitar|first8=Maher|last9=Kwari|first9=Monica I.|date=2002|title=Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients|url=https://ashpublications.org/blood/article/99/3/840/53495/Prognostic-factors-and-scoring-systems-in-chronic|journal=Blood|language=en|volume=99|issue=3|pages=840–849|doi=10.1182/blood.V99.3.840|issn=1528-0020}}</ref>.

==Clinical Features==

|'''Signs and Symptoms'''

|EXAMPLE Asymptomatic (incidental finding on complete blood counts)

 

 

 

|'''Laboratory Findings'''

|EXAMPLE Cytopenias

 

!Finding!!Marker

|Positive (universal)||CD13, CD33

|Positive (variable, can be aberrantly decreased)||CD11c, CD13, CD14, CD15, CD16, CD36, CD64, CD64, CD68, HLA-DR

|-

|Positive (aberrant, variable)

|CD56, CD2. Increased CD34+ blasts suggest disease progression

|-

|Negative (universal)||CD3, CD5, CD20, CD79a (T-cell and B-cell markers)

|Negative (subset)||CD14, CD56

|}

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)

|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)

|Yes

|No

|Yes

|EXAMPLE

 

|}

<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}

<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:

* Gene Mutations (SNV/INDEL)}}

!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

 

|EXAMPLE Loss

|EXAMPLE

 

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

 

|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

 

|EXAMPLE Gain

|EXAMPLE

 

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

 

|No

|No

|No

|EXAMPLE

 

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

<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}

==Characteristic Chromosomal Patterns==

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

!Notes

|EXAMPLE

 

|Yes

|EXAMPLE:

 

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

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

!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

|}

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.

 

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

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>.

Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>

|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

(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''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.''</span> <span style="color:#0070C0">''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''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />

<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.

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