View source for HAEM4Backup:Acute Myeloid Leukemia (AML) with Maturation

==Primary Author(s)*==

Jennelle C. Hodge, PhD, FACMG

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==Cancer Category/Type==

[[AML|Acute Myeloid Leukemia]]

==Cancer Sub-Classification / Subtype==

Acute myeloid leukemia (AML) with maturation

==Definition / Description of Disease==

This is a distinct entity in the World Health Organization (WHO) classification system within the section of [[Acute Myeloid Leukemia (AML), Not Otherwise Specified]]<ref name=":0">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, p158-159.</ref>.  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<ref name=":0" />.

==Synonyms / Terminology==

American-British (FAB) classification M2<ref name=":0" />.

==Epidemiology / Prevalence==

Accounts for 10% of AML, occurring in all ages including 20% in young patients (<25 years old) and 40% in older patients (≥60 years old)<ref name=":0" />.

==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<ref name=":0" />.

==Sites of Involvement==

Bone marrow, Blood

==Morphologic Features==

This AML subtype is characterized by the presence of ≥20% blasts in the bone marrow or blood combined with evidence of maturation in the bone marrow; specifically, ≥10% maturing cells of granulocytic lineage and <20% cells of monocyte lineage<ref name=":0" />.  The blasts may or may not have azurophilic granulation but Auer rods and hypercullularity are typically observed.  Bone marrow cell constitution includes ≥10% promyelocytes, myelocytes and mature nuetrophils, as well as elevated eosinophil precursors which lack the cytological or cytochemical abnormalities characteristic of the abnormal eosinophils in [[Acute Myeloid Leukemia (AML) with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11]].  Basophils and mast calls are sometimes increased, and variable dysplasia occurs but ≤50% of cells in two lineages show dysplasia.

==Immunophenotype==

The characteristic immunophenotype associated with this entity is listed in the table below.  The blasts express one or more of the myeloid-associated antigens, in some cases have a pattern associated with granulocytic differentiation, and typically lack monocytic markers<ref name=":0" />. 

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||Myeloid-associated antigens (CD13, CD33, CD65, CD11b, and/or CD15)
|-
|Positive (subset)||KIT(CD117), CD34 and HLA-DR may be present in some blasts
|-
|Negative (universal)||Monocytic markers (CD14, CD36, CD64)
|-
|Negative (subset)||CD7 (20-30%), CD56, CD2, CD19 and CD4 are uncommon (~10%; may be found only in immature blasts)
|}

==Chromosomal Rearrangements (Gene Fusions)==

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

{| class="wikitable sortable"
|-
!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.

{| class="wikitable sortable"
|-
!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.

{| class="wikitable sortable"
|-
!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===
{| class="wikitable sortable"
|-
!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) MDS with excess blasts in cases with a low blast percentage, 2) AML without Maturation in cases with a high blast percentage, and 3) [[Acute Myelomonocytic Leukemia]] in cases with increased monocytes.  Of note, [[Acute Myeloid Leukemia (AML) with t(8;21)(q22;q22.1);RUNX1-RUNX1T1]] typically has overlapping histologic features as AML with Maturation, but the former should be classified according to its genetic abnormality (i.e. as a subcategory of the entity [[Acute Myeloid Leukemia (AML) with Recurrent Genetic Abnormalities]]).

==Familial Forms==

No familial forms currently known.

==Other Information==

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==Links==

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==References==
<references />

==Notes==
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