The blast cells of patients with AML are most often larger than lymphoblasts and display a greater heterogeneity in size and shape.
AML blast cells have abundant cytoplasm and often contain cytoplasmic granules. Auer rods (azurophilic crystalline-like accumulations of abnormal lysosomal granules visible in the cytoplasm with Wright staining) are detected in about 10% of patients with AML. A diagnosis of AML is established when 20% or more of all the nucleated marrow cells are blast cells.
Classification OMS of acute myeloid leukemia (AML) and related precursor neoplasms
AML with recurrent cytogenetic anomalies
- AML with t(8;21)(q22;q22) (AML1/ETO fusion gene)
- AML with inv(16)(p13q22) or t(16;16)(p13;q22) (CBFB/MYH11 gene fusion)
- Acute promyelocytic leukemia with t(15;17)(q22;q12); PML-RARA
- AML with t(9 ;11)(p22;q23); MLLT3-MLL
- AML with t(6;9)(p23;q34); DEK-NUP214
- AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1
- AML with mutated NPM1*
- AML with mutated CEBPA*
- AML with 11q23 rearrangements (MLL-associated leukemias)
AML with myelodysplasia-related changes
therapy-related myeloid neoplasms and myelodysplastic syndrome
- alkylating agent-related AML and myelodysplastic syndrome
- topoisomerase II inhibitor-related AML and myelodysplastic syndrome
myeloid sarcoma
trisomy-21 associated myeloid proliferations (Down syndrome)
- trisomy-21 associated transient abnormal myelopoiesis
- trisomy-21 associated myeloid leukemia
blastic plasmacytoid dendritic cell neoplasm
Other categories
AML with multilineage dysplasia
- with prior myelodysplastic syndrome
- without prior myelodysplastic syndrome
AML not otherwise categorised
- minimally differentiated acute myeloid leukemia
- acute myeloid leukemia without maturation
- acute myeloid leukemia with maturation
- acute myelomonocytic leukemia
- acute monoblastic leukemia and acute monocytic leukemia
- acute erythroid leukemia (AML M6)
- acute megakaryoblastic leukemia (AML M7)
- acute basophilic leukemia
- acute panmyelosis with myelofibrosis
(*: Provisional entities)
FAB classification
| AML-MO | AML-M1 | AML-M2 | AML-M3 | AML-M4 | AML-M5 | AML-M6 | AML-M7 |
The FAB group defined eight variants of AML, including three types with predominantly granulocytic differentiation (M1, M2, and M3), two with at least 20% monocytic precursors (M4 and M5), one with a high proportion of erythroblasts (M6), and a more recently recognized and rarely occurring variant with predominance of megakaryoblasts (M7).
In addition, the FAB group described a form of AML with minimal myeloid differentiation, designated M0, which cannot be diagnosed solely on morphologic or cytochemical grounds but requires the added use of immunohistochemical staining. AML M0 blast cells express myeloid antigens on their surface but lack myeloperoxidase reactivity.
Molecular biology
Four genes had been found to be fused to a variety of partner genes in AML:
AML1 (RUNX1) (MIM.151385)
MOZ (MIM.601408)
TEL (ETV6) (MIM.600618)
NUP98 (MIM.601021) - NUP98/HOXD11 by t(2;11)(q31;p15) (MIM.142986) - NUP98/HOXD13 (MIM.142989)
11q23 - MLL
Translocations involving 11q23 are acute monoblastic leukemia (AML-M5) and acute myelomonocytic leukemia (AMML-M4)
MLL/GMPS
MLL/FBP17
MLL/LPP
MLL/GPH
MLL/PNUTL1
MLL/CDK6
MLL/LASP1
MLL/GRAF
MLL/ABI1
MLL/AF9 fusion gene from translocation t(9;11)(p22;q23)
Cytogenetics
References
Lindvall C, Furge K, Björkholm M, Guo X, Haab B, Blennow E, Nordenskjöld M, Teh BT. Combined genetic and transcriptional profiling of acute myeloid leukemia with normal and complex karyotypes. Haematologica. 2004 Sep;89(9):1072-81. PMID: 15377468
Reviews
New classification of acute myeloid leukemia and precursor-related neoplasms: changes and unsolved issues. Falini B, Tiacci E, Martelli MP, Ascani S, Pileri SA. Discov Med. 2010 Oct;10(53):281-92. PMID: 21034669 [Free]
Licht JD, Sternberg DW. The molecular pathology of acute myeloid leukemia. Hematology Am Soc Hematol Educ Program 2005:137-42.
Nerlov C. C/EBPalpha mutations in acute myeloid leukaemias. Nat Rev Cancer. 2004 May;4(5):394-400. PMID: 15122210
Tenen DG. Disruption of differentiation in human cancer: AML shows the way. Nat Rev Cancer. 2003 Feb;3(2):89-101. PMID: 12563308
Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002 Oct 1;100(7):2292-302. PMID: 12239137