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Table 3 Evolution of AML tabulation from the 1970s with the advent of FAB classification method and the following development of WHO and ELN classification. Table improved and revised from [20]

From: Acute myeloid leukemia: from NGS, through scRNA-seq, to CAR-T. dissect cancer heterogeneity and tailor the treatment

Classification schemes for acute myeloid leukemia (AML)

French-American-British (FAB) classification

1. AML subtypes were defined on the basis of morphologic features and cytochemical methods, categorized as M0 through M7

 • M0-M5: include leukemia involving myeloid blasts with varying degree of maturation

 • M6: acute erythroid leukemia

 • M7: acute megakaryocytic leukemia

 • M3: represents the distinct subtype of acute promyelocytic leukemia (APL)

2. FAB criteria evidenced M2 (25%) and M4 (20%) as the most common subtypes disease

World Health Organization (WHO) classification

1. AML with recurrent genetic abnormalities

 • AML with t(8;21)(q22q22.1); 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); KMT2A-MLLT3

 • 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;q13.1); RBM15-MKL1

 • Provisional entity: AML with BCR-ABL1

 • AML with mutated NPM1

 • AML with biallelic mutation of CEBPA

 • Provisional entity: AML with mutated RUNX1

2. AML with myelodysplasia-related changes

3. Therapy-related myeloid neoplasms

4. AML, not otherwise specified (NOS)

 • AML with minimal differentiation

 • AML without maturation

 • AML with maturation

 • Acute myelomonocytic leukemia

 • Acute monoblastic and monocytic leukemia

 • Pure erythroid leukemia

 • Acute megakaryoblastic leukemia

 • Acute basophilic leukemia

 • Acute panmyelosis with myelofibrosis

5. Myeloid sarcoma

6. Myeloid proliferations associated with Down syndrome

 • Transient abnormal myelopoiesis (TAM) associated with Down Syndrome

 • Myeloid leukemia associated with Down Syndrome

European Leukemia-Net (ELN) classification

1. The favorable category includes:

 • Core binding factor AML, defined by the cytogenetic abnormalities t(8;21)(q22;q22.1) RUNX1-RUNX1T1; inv(16)(p13.1q22) or t(16;16)(p13.1;q22) CBFB-MYH11;

 • It is implicated also the favorable prognosis of AML with NPM1 or biallelic mutated CEBPA, disregarding the concomitant presence of gene mutations.

 • Similar favorable impact noticed of NPM1; in frame mutations of basic basic leucine Zipper (bZIP) region of CEBPA

2. The intermediate classification includes:

 • Those cytogenetic and/or abnormalities not classified as favorable or adverse

 • Mutated NPM1 in presence of FLT3-ITD

 • Wild type NPM1 with FLT3-ITD (without adverse-risk genetic lesions

 • t(9;11) (p21.3;q23.3), MLLT3-KMT2A aberrations

3. The adverse risk subtype includes:

 • The high risk mutation TP53 (with VAF ≥ 10%) and mutations in RUNX1, ASXL1, EZH2, SF3B1, SRSF2, STAG2, U2AF1 and ZRSR2 (not coexisting with favorable risk subtypes)

 • Wild type NPM1 with FLT3-ITD high allelic ratio (> 0.5) carries a poor prognosis and it is also comprised in the adverse risk group

 • Monosomal or complex karyotypes (≥ 3unrelated chromome bnormalities)

 • Specific cytogenetic markers of high risk disease including t(6;9)(p23;q34.1) / DEK-NUP214, t(v;11q23.3) / KMT2A rearranged, t(9;22)(q34.1;q11.2) / BCR-ABL1, inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2), GATA2, MECOM(EVI1), monosomy 5 or del(5q), monosomy 7, − 17 / abn (17q)