Acute myeloid leukaemia without maturation

Haematolymphoid Tumours (WHO Classification, 5th ed.)

editHAEM5 Conversion Notes

This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Acute Myeloid Leukemia (AML) without Maturation.

(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click nearby within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)

Primary Author(s)*

Jennelle C. Hodge, PhD, FACMG

Cancer Category / Type

Acute Myeloid Leukemia

Cancer Sub-Classification / Subtype

Acute myeloid leukemia (AML) without maturation

Definition / Description of Disease

This is a distinct entity in the World Health Organization (WHO) classification system 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). There is currently no known recurrent chromosomal abnormality associated with this entity.

Synonyms / Terminology

American-British (FAB) classification M1 [1].

Epidemiology / Prevalence

Accounts for 5-10% of AML, occurring mostly in adults (median age of ~46 years).

Clinical Features

Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete 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)

editHAEM5 Conversion Notes

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

Usually presents with symptoms of bone marrow failure, including anemia, thrombocytopenia and neutropenia. There is also variability in the white blood cell and blast counts, which can include leukocytosis with markedly increased blasts.

Sites of Involvement

Bone marrow

Morphologic Features

This AML subtype is characterized by the presence in the bone marrow of a high percentage of myeloid blasts without significant evidence of maturation; specifically, <10% of the nucleated bone marrow cells represent maturing cells of the granulocytic lineage. Cases are typically markedly hypercellular (range also includes normocellular and hypocellular) and can involve myeloblasts with azurophilic granules and/or Auer rods, while other cases present with cells resembling lymphoblasts that lack azurophilic granules.

Immunophenotype

The characteristic immunophenotype associated with this entity is listed in the table below. The myeloid nature of the blasts includes an immunophenotype positive for MPO or SBB in ≥3% of the blasts and/or the presence of Auer rods, as well as typically positivity for one or more myeloid-associated antigens.

Finding	Marker
Positive (universal)	Myeloperoxidase (MPO), Sudan Black B (SBB), one or more of CD13, CD33 and/or KIT(CD117)
Positive (subset)	CD34 and HLA-DR (only 70%), CD11b
Negative (universal)	Granulocytic maturation markers (CD15, CD65), Monocytic markers (CD14, CD64), B-cell and T-cell cytoplasmic lymphoid markers (cCD3, cCD79a, cCD22)
Negative (subset)	CD7 (only 30%), Lymphoid-associated membrane markers (CD2, CD4, CD19, CD56; only 10-20%)

Chromosomal Rearrangements (Gene Fusions)

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)	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).

editHAEM5 Conversion Notes

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

There is currently no known recurrent chromosomal abnormality associated with this entity.

Chromosomal Rearrangement	Genes in Fusion (5’ or 3’ Segments)	Pathogenic Derivative	Prevalence
EXAMPLE: t(9;22)(q34;q11.2)	EXAMPLE: 3'ABL1 / 5'BCR	EXAMPLE: der(22)	EXAMPLE: 5%
EXAMPLE: t(8;21)(q22;q22)	EXAMPLE: 5'RUNX1 / 3'RUNXT1	EXAMPLE: der(8)	EXAMPLE: 5%

editHAEM5 Conversion Notes

Please incorporate this section into the relevant tables found in:

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

The differential diagnosis includes 1) Lymphoblastic Leukemia in the presence of blast cells lacking granules or in cases with a low percentage of MPO-positive blasts and 2) AML with Maturation in cases with a higher percentage of MPO-positive blasts.

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. Do not delete table.)

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).

editHAEM5 Conversion Notes

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

There is currently no known recurrent chromosomal abnormality associated with this entity.

Chromosome Number	Gain/Loss/Amp/LOH	Region
EXAMPLE: 8	EXAMPLE: Gain	EXAMPLE: chr8:0-1000000
EXAMPLE: 7	EXAMPLE: Loss	EXAMPLE: chr7:0-1000000

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. Do not delete table.)

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).

editHAEM5 Conversion Notes

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

There is currently no known recurrent chromosomal abnormality associated with this entity.

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 as 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. Do not delete table.)

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.

editHAEM5 Conversion Notes

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

Currently there is currently no known recurrent gene mutations associated with this entity.

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

Not applicable

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Can include references in the table. Do not delete table.)

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

editHAEM5 Conversion Notes

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

Unknown

Genetic Diagnostic Testing Methods

Histology and immunophenotype

Familial Forms

No familial forms currently known.

Additional Information

Put your text here

Links

Put your links here

References

(use the "Cite" icon at the top of the page) (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. 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.)

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 myeloid leukaemia without maturation”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/1/2024, https://ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_without_maturation.