Acute Myeloid Leukemia (AML) without Maturation
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Primary Author(s)*
Jennelle C. Hodge, PhD, FACMG
Cancer Category/Type
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[1]. 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[1].
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)[1].
Clinical Features
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[1].
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[1]. 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[1].
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[1].
| 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)
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% |
Characteristic Chromosomal Aberrations / Patterns
There is currently no known recurrent chromosomal abnormality associated with this entity.
Genomic Gain/Loss/LOH
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 |
Gene Mutations (SNV/INDEL)
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 |
Epigenomics (Methylation)
Not applicable
Genes and Main Pathways Involved
Unknown
Diagnostic Testing Methods
Histology and immunophenotype
Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)
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[1].
Familial Forms
No familial forms currently known.
Other Information
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Links
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References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. 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. IARC Press: Lyon, France, p157-158.
Notes
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