Classification of acute myeloid leukemia
- Charles A Schiffer, MD
Charles A Schiffer, MD
- Professor of Medicine and Oncology
- Barbara Ann Karmanos Cancer Institute
- Wayne State University School of Medicine
- Sandeep Gurbuxani, MBBS, PhD
Sandeep Gurbuxani, MBBS, PhD
- Associate Professor, Section of Hematopathology, Department of Pathology
- University of Chicago
Acute myeloid leukemia (AML) consists of a group of relatively well-defined hematopoietic neoplasms involving precursor cells committed to the myeloid line of cellular development (ie, those giving rise to granulocytic, monocytic, erythroid, or megakaryocytic elements) (table 1). AML has also been called acute myelogenous leukemia and acute non-lymphocytic leukemia.
AML is characterized by a clonal proliferation of myeloid precursors with a reduced capacity to differentiate into more mature cellular elements. As a result, there is an accumulation of leukemic blasts or immature forms in the bone marrow, peripheral blood, and occasionally in other tissues, with a variable reduction in the production of normal red blood cells, platelets, and mature granulocytes. The increased production of malignant cells, along with a reduction in these mature elements, results in a variety of systemic consequences including anemia, bleeding, and an increased risk of infection. (See "Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia" and "Pathogenesis of acute myeloid leukemia".)
Following diagnosis, AML is classified using the World Health Organization (WHO) classification system based upon a combination of morphology, immunophenotype, genetics, and clinical features [1-3]. The classification attempts to identify biologic entities in the hopes that future work will elucidate molecular pathways that might be amenable to targeted therapies.
There are six main groups of AML recognized in this classification system [1,3-5]:
●AML with recurrent genetic abnormalities
- Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009; 114:937.
- Swerdlow SH, Campo E, Harris NL, et al. (Eds). World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.
- Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127:2391.
- Dores GM, Devesa SS, Curtis RE, et al. Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007. Blood 2012; 119:34.
- Grimwade D, Hills RK, Moorman AV, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 2010; 116:354.
- Nucifora G, Rowley JD. AML1 and the 8;21 and 3;21 translocations in acute and chronic myeloid leukemia. Blood 1995; 86:1.
- Bennett JM, Catovsky D, Daniel MT, et al. Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. Ann Intern Med 1985; 103:620.
- Bitter MA, Le Beau MM, Rowley JD, et al. Associations between morphology, karyotype, and clinical features in myeloid leukemias. Hum Pathol 1987; 18:211.
- Peniket A, Wainscoat J, Side L, et al. Del (9q) AML: clinical and cytological characteristics and prognostic implications. Br J Haematol 2005; 129:210.
- Holmes R, Keating MJ, Cork A, et al. A unique pattern of central nervous system leukemia in acute myelomonocytic leukemia associated with inv(16)(p13q22). Blood 1985; 65:1071.
- Ohyashiki K, Ohyashiki JH, Iwabuchi A, et al. Central nervous system involvement in acute nonlymphocytic leukemia with inv(16)(p13q22). Leukemia 1988; 2:398.
- Schwind S, Edwards CG, Nicolet D, et al. inv(16)/t(16;16) acute myeloid leukemia with non-type A CBFB-MYH11 fusions associate with distinct clinical and genetic features and lack KIT mutations. Blood 2013; 121:385.
- Larson RA, Kondo K, Vardiman JW, et al. Evidence for a 15;17 translocation in every patient with acute promyelocytic leukemia. Am J Med 1984; 76:827.
- Melnick A, Licht JD. Deconstructing a disease: RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. Blood 1999; 93:3167.
- Forestier E, Heim S, Blennow E, et al. Cytogenetic abnormalities in childhood acute myeloid leukaemia: a Nordic series comprising all children enrolled in the NOPHO-93-AML trial between 1993 and 2001. Br J Haematol 2003; 121:566.
- Chi Y, Lindgren V, Quigley S, Gaitonde S. Acute myelogenous leukemia with t(6;9)(p23;q34) and marrow basophilia: an overview. Arch Pathol Lab Med 2008; 132:1835.
- Gröschel S, Sanders MA, Hoogenboezem R, et al. A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia. Cell 2014; 157:369.
- Yamazaki H, Suzuki M, Otsuki A, et al. A remote GATA2 hematopoietic enhancer drives leukemogenesis in inv(3)(q21;q26) by activating EVI1 expression. Cancer Cell 2014; 25:415.
- Pintado T, Ferro MT, San Román C, et al. Clinical correlations of the 3q21;q26 cytogenetic anomaly. A leukemic or myelodysplastic syndrome with preserved or increased platelet production and lack of response to cytotoxic drug therapy. Cancer 1985; 55:535.
- Bitter MA, Neilly ME, Le Beau MM, et al. Rearrangements of chromosome 3 involving bands 3q21 and 3q26 are associated with normal or elevated platelet counts in acute nonlymphocytic leukemia. Blood 1985; 66:1362.
- Chang VT, Aviv H, Howard LM, Padberg F. Acute myelogenous leukemia associated with extreme symptomatic thrombocytosis and chromosome 3q translocation: case report and review of literature. Am J Hematol 2003; 72:20.
- World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Swerdlow SH, Campo E, Harris NL (Eds), IARC Press, Lyon 2008.
- Atfy M, Al Azizi NM, Elnaggar AM. Incidence of Philadelphia-chromosome in acute myelogenous leukemia and biphenotypic acute leukemia patients: And its role in their outcome. Leuk Res 2011; 35:1339.
- Nacheva EP, Grace CD, Brazma D, et al. Does BCR/ABL1 positive acute myeloid leukaemia exist? Br J Haematol 2013; 161:541.
- Falini B, Macijewski K, Weiss T, et al. Multilineage dysplasia has no impact on biologic, clinicopathologic, and prognostic features of AML with mutated nucleophosmin (NPM1). Blood 2010; 115:3776.
- Cancer Genome Atlas Research Network, Ley TJ, Miller C, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 2013; 368:2059.
- Chen CY, Lin LI, Tang JL, et al. RUNX1 gene mutation in primary myelodysplastic syndrome--the mutation can be detected early at diagnosis or acquired during disease progression and is associated with poor outcome. Br J Haematol 2007; 139:405.
- Tang JL, Hou HA, Chen CY, et al. AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations. Blood 2009; 114:5352.
- Schnittger S, Dicker F, Kern W, et al. RUNX1 mutations are frequent in de novo AML with noncomplex karyotype and confer an unfavorable prognosis. Blood 2011; 117:2348.
- Weinberg OK, Seetharam M, Ren L, et al. Clinical characterization of acute myeloid leukemia with myelodysplasia-related changes as defined by the 2008 WHO classification system. Blood 2009; 113:1906.
- Haferlach C, Mecucci C, Schnittger S, et al. AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features. Blood 2009; 114:3024.
- Schlenk RF, Taskesen E, van Norden Y, et al. The value of allogeneic and autologous hematopoietic stem cell transplantation in prognostically favorable acute myeloid leukemia with double mutant CEBPA. Blood 2013; 122:1576.
- Miesner M, Haferlach C, Bacher U, et al. Multilineage dysplasia (MLD) in acute myeloid leukemia (AML) correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: a comparison of 408 cases classified as "AML not otherwise specified" (AML-NOS) or "AML with myelodysplasia-related changes" (AML-MRC). Blood 2010; 116:2742.
- Walter RB, Othus M, Burnett AK, et al. Significance of FAB subclassification of "acute myeloid leukemia, NOS" in the 2008 WHO classification: analysis of 5848 newly diagnosed patients. Blood 2013; 121:2424.
- Lee EJ, Pollak A, Leavitt RD, et al. Minimally differentiated acute nonlymphocytic leukemia: a distinct entity. Blood 1987; 70:1400.
- Béné MC, Bernier M, Casasnovas RO, et al. Acute myeloid leukaemia M0: haematological, immunophenotypic and cytogenetic characteristics and their prognostic significance: an analysis in 241 patients. Br J Haematol 2001; 113:737.
- Roumier C, Eclache V, Imbert M, et al. M0 AML, clinical and biologic features of the disease, including AML1 gene mutations: a report of 59 cases by the Groupe Français d'Hématologie Cellulaire (GFHC) and the Groupe Français de Cytogénétique Hématologique (GFCH). Blood 2003; 101:1277.
- Haferlach T, Schoch C, Schnittger S, et al. Distinct genetic patterns can be identified in acute monoblastic and acute monocytic leukaemia (FAB AML M5a and M5b): a study of 124 patients. Br J Haematol 2002; 118:426.
- Swerdlow SH, Campo E, Harris NL, et al. World Health Organization classification of tumours of haematopoietic and lymphoid tissues, IARC Press, Lyon 2008.
- Tallman MS, Neuberg D, Bennett JM, et al. Acute megakaryocytic leukemia: the Eastern Cooperative Oncology Group experience. Blood 2000; 96:2405.
- Dastugue N, Lafage-Pochitaloff M, Pagès MP, et al. Cytogenetic profile of childhood and adult megakaryoblastic leukemia (M7): a study of the Groupe Français de Cytogénétique Hématologique (GFCH). Blood 2002; 100:618.
- Oki Y, Kantarjian HM, Zhou X, et al. Adult acute megakaryocytic leukemia: an analysis of 37 patients treated at M.D. Anderson Cancer Center. Blood 2006; 107:880.
- Gruber TA, Downing JR. The biology of pediatric acute megakaryoblastic leukemia. Blood 2015; 126:943.
- Ma Z, Morris SW, Valentine V, et al. Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nat Genet 2001; 28:220.
- Zipursky A. Transient leukaemia--a benign form of leukaemia in newborn infants with trisomy 21. Br J Haematol 2003; 120:930.
- Sorrell AD, Alonzo TA, Hilden JM, et al. Favorable survival maintained in children who have myeloid leukemia associated with Down syndrome using reduced-dose chemotherapy on Children's Oncology Group trial A2971: a report from the Children's Oncology Group. Cancer 2012; 118:4806.
- AML WITH RECURRENT GENETIC ABNORMALITIES
- Defined structural abnormalities
- - AML with t(8;21)(q22;q22); RUNX1-RUNX1T1
- - AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
- - APL with PML-RARA
- - AML with t(9;11)(p21.3;q23.3); MLLT3-KMT2A
- - AML with t(6;9)(p23;q34.1); DEK-NUP214
- - AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2,MECOM
- - AML (megakaryoblastic) with t(1;22)(p13.3;q13.3); RBM15-MKL1
- - AML with BCR-ABL1
- AML with gene mutations
- - AML with mutated NPM1
- - AML with biallelic mutations of CEBPA
- - AML with mutated RUNX1
- AML WITH MDS-RELATED FEATURES
- THERAPY-RELATED AML
- AML NOT OTHERWISE SPECIFIED
- AML with minimal differentiation (FAB M0)
- AML without maturation (FAB M1)
- AML with maturation (FAB M2)
- Acute myelomonocytic leukemia (FAB M4)
- Acute monoblastic and monocytic leukemia (FAB M5)
- Pure erythroid leukemia (FAB M6)
- Acute megakaryoblastic leukemia (FAB M7)
- Acute basophilic leukemia
- Acute panmyelosis with myelofibrosis
- MYELOID SARCOMA
- MYELOID PROLIFERATIONS RELATED TO DOWN SYNDROME