Acute monocytic leukaemia

Haematolymphoid Tumours (WHO Classification, 5th ed.)

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Primary Author(s)*

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

Cancer Category / Type

Acute Myeloid Leukemia

Cancer Sub-Classification / Subtype

Acute monoblastic and monocytic leukemia

Definition / Description of Disease

Acute monoblastic and monocytic leukemia are myeloid leukemias in which the peripheral blood or bone marrow has ≥20% blasts (including promonocytes) and in which ≥80% of the leukemic cells are of monocytic lineage (monoblasts, promonocytes and monocytes). Neutrophils may be noted (<20%). In acute monoblastic leukemia, most (≥80%) of the monocytic cells are monoblasts; while in acute monocytic leukemia, most of the monocytic cells are promonocytes or monocytes. In the 2016 revision to the World Health Organization (WHO) classification system, acute monoblastic and monocytic 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

Acute monoblastic leukemia; acute monocytic leukemia; French-American-British (FAB) classification M5, Monoblastic leukemia NOS

Epidemiology / Prevalence

Acute monoblastic leukemia:

• less than 5% of AML cases
• more common in young individuals

Acute monocytic leukemia:

• less than 5% of AML cases
• more common in adults; the median patient age is 49 years
• the male-to-female ratio is 1.8:1

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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• Common manifestations include extramedullary masses, lymphadenopathy, cutaneous and gingival infiltration, CNS involvement and presenting with bleeding disorders
• May present with acute respiratory failure

Sites of Involvement

Bone marrow; extramedullary sites such as lymph nodes, skin, gingiva, and CNS.

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 and vacuoles may be present.
• Promonocytes have a more irregular and delicately convoluted nuclear configuration and cytoplasm which is usually less basophillic and more granulated.
• Hemophagocytosis (erythrophagocytosis) may be observed, often associated with t(8;16)(p11.2;p13.3).
• The extramedullary lesion may be composed mainly of monoblasts, promocytes or both.

Immunophenotype

Cytochemistry

• Monoblast granules and monocytes are strongly positive for non-specific esterase and lysozyme in most cases
• Monoblasts are typically negative for myeloperoxidase (MPO), although promonocytes may have scattered positivity.

Often a complex immunophenotype with multiple blast populations including:

• immature blasts with CD34 (30% of cases) and/or KIT (CD117) expression
• populations with myeloid markers: CD13, CD33, CD15, CD65
• populations with at least two monocytic markers: CD4, CD14, CD11b, CD11c, CD64, CD36, CD68, and lysozyme
• most cases are positive for HLA-DR
• MPO can be expressed in acute monocytic leukemia and less often in monoblastic leukemia

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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Chromosomal Rearrangement	Genes in Fusion (5’ or 3’ Segments)	Pathogenic Derivative	Prevalence
t(8;16)(p11.2;p13.3)	5'KAT6A / 3'CREBBP or 5'CREBBP / 3'KAT6A	der(8) or der(16)	0.2% of AML

editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).

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• Chromosomal Rearrangements (Gene Fusions)
• Individual Region Genomic Gain/Loss/LOH
• Characteristic Chromosomal Patterns
• Gene Mutations (SNV/INDEL)

Diagnosis

• The main differential diagnoses of acute monoblastic leukemia include: AML without maturation, AML with minimal differentiation, AML with t(9;11)(p21.3;q23.3), and acute megakaryoblastic leukemia (AMKL). Extramedullary monoblastic sarcoma needs to be differentiated from malignant lymphoma or soft tissue sarcomas.
• The main differential diagnoses of acute monocytic leukemia include: chronic myelomonocytic leukemia, acute myelomonocytic leukemia, and microgranular acute promyelocytic leukamia (APL).
• Haemophagocytosis (erythrophagocytosis) with t(8;16)(p11.2;p13.3) may also occur in acute myelomonocytic leukemia and some cases of AML with maturation.

Prognosis

• Multiple studies have shown that t(8;16)(p11.2;p13.3) positive AML usually has a poor prognosis.

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).

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 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.

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

Genetic Diagnostic Testing Methods

• Conventional chromosome analysis
• FISH myeloid panel
• FISH or RT-PCR for KAT6A-CREBBP gene rearrangement

Familial Forms

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Additional Information

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Links

http://atlasgeneticsoncology.org/Anomalies/t0816ID1018.html

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 monocytic leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/6/2024, https://ccga.io/index.php/HAEM5:Acute_monocytic_leukaemia.