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acute myeloid leukemias

Monday 9 June 2003

Digital slides

- UI:500 - Acute myeloid leukemia
- UI:1008 - Acute myeloid leukemia with inv(16) and increased abnormal eosinophils

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)

- MLL (MIM.159555)

- 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, Bj√∂rkholm M, Guo X, Haab B, Blennow E, Nordenskj√∂ld 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


- MIM.601626