Acute myelomonocytic leukaemia

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Haematolymphoid Tumours (5th ed.)

editHAEM5 Conversion Notes
This page was converted to the new template on 2023-11-03. The original page can be found at HAEM4:Acute Myelomonocytic Leukemia.

Primary Author(s)*

Fei Yang, MD, FACMG
Oregon Health & Science University, Portland, OR

Cancer Category/Type

Acute Myeloid Leukemia

Cancer Sub-Classification / Subtype

Acute myelomonocytic leukemia

Definition / Description of Disease

Acute myelomonocytic leukemia is an acute leukemia characterized by the proliferation of both neutrophil and monocyte precursors. The peripheral blood or bone marrow has more than 20% blasts (including promonocytes). A minimum of 20% monocytes and their precursors is required for the morphological diagnosis, differentiating this entity from cases of AML with or without maturation that can present with a low-level of monocytes. In the 2016 revision to the World Health Organization (WHO) classification system, acute myelomonocytic leukemia is a distinct entity within the section of Acute Myeloid Leukemia (AML), Not Otherwise Specified[1][2]. This entity does not meet the criteria for inclusion in any of the other AML groups (i.e. AML with Recurrent Genetic Abnormalities, AML with Myelodysplasia-Related Changes, or Therapy-Related Myeloid Neoplasms).

Synonyms / Terminology

French-American-Brirish (FAB) classification M4, NOS

Epidemiology / Prevalence

Approximately 5-10% of AML cases, 3% of childhood leukemia

  • occurs in all age groups, but is more common in older individuals.
  • median patient age is 50 years
  • male-to-female ratio is 1.4:1

Clinical Features

Put your text here and fill in the table (Instruction: Can include references in the 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 Features
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The common clinical presentations are related to anaemia and thrombocytopenia, including fever, pallor, dyspnea, fatigue, loss of weight and bleeding disorders.

Sites of Involvement

Bone marrow

Morphologic Features

  • Monoblasts are large cells with abundant cytoplasm, which can be moderately to intensely basophillic, and round nuclei with delicate lacy chromatin and one or more predominant nucleoli; scattered azurophillic granuoles, vacuoles, and Auer rods may be present.
  • Promonocytes have a more irregular and delicately convoluted nuclear configuration and cytoplasm which is usually less basophillic and more granulated.
  • The peripheral blood typically shows an increase in monocytes, which are often more mature than those in the bone marrow.

Immunophenotype

Cytochemistry

  • ≥3% of blasts show myeloperoxidase (MPO) activity.
  • Monoblasts, promonocytes and monocytes usually show non-specific esterase activity.

Often a complex immunophenotype with multiple blast populations seen including:

  • immature blasts with high CD34 and/or KIT (CD117) expression
  • populations with myeloid markers: CD13, CD33, CD15, CD65 and MPO
  • populations with monocytic markers: CD4, CD11b, CD11c, CD14, CD64, CD36, CD68 (PGM1), CD163 and lysozyme
  • most cases are positive for HLA-DR
  • approximately 30% of cases are positive for CD7
Finding Marker
Positive (universal) EXAMPLE CD1
Positive (subset) EXAMPLE CD2
Negative (universal) EXAMPLE CD3
Negative (subset) EXAMPLE CD4

Chromosomal Rearrangements (Gene Fusions)

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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)
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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.)

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).

editv4:Genomic Gain/Loss/LOH
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None

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)

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 / Patterns
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Myeloid-associated nonspecific cytogenetic abnormalities, such as trisomy 8, are present in most cases.

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 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.)

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)
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Acute myelomonocytic leukemia has genetic heterogeneity at the molecular level. Currently there is no specific gene identified that is frequently associated with this subset of AML.

Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other)
EXAMPLE TP53 EXAMPLE R273H EXAMPLE Tumor Suppressor EXAMPLE LOF EXAMPLE 20%

Other Mutations

Type Gene/Region/Other
Concomitant Mutations EXAMPLE IDH1 R123H
Secondary Mutations EXAMPLE Trisomy 7
Mutually Exclusive EXAMPLE EGFR Amplification

Epigenomic Alterations

None

Genes and Main Pathways Involved

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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 Involved
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None

Genetic Diagnostic Testing Methods

  • Conventional chromosome analysis
  • FISH myeloid panel

Familial Forms

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Additional Information

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Links

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References

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  1. 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. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. IARC Press: Lyon, France, p159-160.
  2. Arber, Daniel A.; et al. (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 1528-0020. PMID 27069254.

Notes

*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. *Citation of this Page: “Acute myelomonocytic leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 11/3/2023, https://ccga.io/index.php/HAEM5:Acute_myelomonocytic_leukaemia.