HAEM5:Acute myelomonocytic leukaemia

Haematolymphoid Tumours (WHO Classification, 5th ed.)

editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification

This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Acute Myelomonocytic Leukemia.

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Primary Author(s)*

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

WHO Classification of Disease

Structure	Disease
Book	Haematolymphoid Tumours (5th ed.)
Category	Myeloid proliferations and neoplasms
Family	Acute myeloid leukaemia
Type	Acute myeloid leukaemia, defined by differentiation
Subtype(s)	Acute myelomonocytic leukaemia

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 HAEM4:Acute Myeloid Leukemia (AML), Not Otherwise Specified. 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

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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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• None
• if inv(16)(p13.1q22) or t(16;16)(p13.1;q22) are present, classify as HAEM4:Acute Myeloid Leukemia (AML) with Recurrent Genetic Abnormalities: HAEM5:Acute myeloid leukaemia with CBFB::MYH11 fusion.

Individual Region Genomic Gain / Loss / LOH

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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

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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)

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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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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 09/6/2024, https://ccga.io/index.php/HAEM5:Acute_myelomonocytic_leukaemia.