ACUTE MYELOID LEUKEMIA (AML)

ACUTE MYELOID LEUKEMIA (AML) is a topic covered in the Harrison's Manual of Medicine.

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AML is a clonal malignancy of myeloid bone marrow precursors in which poorly differentiated cells accumulate in the bone marrow and circulation.

Signs and symptoms occur because of the absence of mature cells normally produced by the bone marrow, including granulocytes (susceptibility to infection) and platelets (susceptibility to bleeding). In addition, if large numbers of immature malignant myeloblasts circulate, they may invade organs and rarely produce dysfunction. There are distinct morphologic subtypes (Table 66-1) that have largely overlapping clinical features. Of note is the propensity of pts with acute promyelocytic leukemia (APL) (FAB M3) to develop bleeding and disseminated intravascular coagulation, especially during induction chemotherapy, because of the release of procoagulants from their cytoplasmic granules.

TABLE 66-1: AML Classification Systems
World Health Organization classificationa
AML with recurrent genetic abnormalities
 AML with t(8;21)(q22;q22); RUNX1-RUNX1T1b
 AML with inv(16)(p13.1;1q22) or t(16;16)(p13.1;q22); CBFB-MYH11b
 Acute promyelocytic leukemia with t(15;17)(q22;q12); PML-RARAb
 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 (megakaryoblastic) with t(1;22)(p13;q13); RBM15-MKL1
 Provisional entity: AML with mutated NPM1
 Provisional entity: AML with mutated CEBPA
AML with myelodysplasia-related changes
Therapy-related myeloid neoplasms
AML not otherwise specified
 AML with minimal differentiation
 AML without maturation
 AML with maturation
 Acute myelomonocytic leukemia
 Acute monoblastic and monocytic leukemia
 Acute erythroid leukemia
 Acute megakaryoblastic leukemia
 Acute basophilic leukemia
 Acute panmyelosis with myelofibrosis
Myeloid sarcoma
Myeloid proliferations related to Down syndrome
 Transient abnormal myelopoiesis
 Myeloid leukemia associated with Down syndrome
Blastic plasmacytoid dendritic cell neoplasm
Acute leukemia of ambiguous lineage
 Acute undifferentiated leukemia
 Mixed phenotype acute leukemia with t(9;22)(q34;q11,20); BCR-ABL11
 Mixed phenotype acute leukemia with t(v;11q23); MLL rearranged
 Mixed phenotype acute leukemia, B/myeloid, NOS
 Mixed phenotype acute leukemia, T/myeloid, NOS
 Provisional entity: Natural killer (NK)-cell lymphoblastic leukemia/lymphoma
French-American-British (FAB) classificationc
 MO: Minimally differentiated leukemia
 Ml: Myeloblastic leukemia without maturation
 M2: Myeloblastic leukemia with maturation
 M3: Hypergranular promyelocytic leukemia
 M4: Myelomonocytic leukemia
 M4Eo: Variant: Increase in abnormal marrow eosinophils
 M5: Monocytic leukemia
 M6: Erythroleukemia (DiGuglielmo’s disease)
 M7: Megakaryoblastic leukemia
aData from Swerdlow SH et al (eds): World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, 4th edition update, IARC Press, 2017.
bDiagnosis is AML regardless of blast count.
cData from Bennett JM et al: Proposed revised criteria for the classification of acute myeloid leukemia. Ann Intern Med 103:620, 1985.
Abbreviation: AML, acute myeloid leukemia.

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AML is a clonal malignancy of myeloid bone marrow precursors in which poorly differentiated cells accumulate in the bone marrow and circulation.

Signs and symptoms occur because of the absence of mature cells normally produced by the bone marrow, including granulocytes (susceptibility to infection) and platelets (susceptibility to bleeding). In addition, if large numbers of immature malignant myeloblasts circulate, they may invade organs and rarely produce dysfunction. There are distinct morphologic subtypes (Table 66-1) that have largely overlapping clinical features. Of note is the propensity of pts with acute promyelocytic leukemia (APL) (FAB M3) to develop bleeding and disseminated intravascular coagulation, especially during induction chemotherapy, because of the release of procoagulants from their cytoplasmic granules.

TABLE 66-1: AML Classification Systems
World Health Organization classificationa
AML with recurrent genetic abnormalities
 AML with t(8;21)(q22;q22); RUNX1-RUNX1T1b
 AML with inv(16)(p13.1;1q22) or t(16;16)(p13.1;q22); CBFB-MYH11b
 Acute promyelocytic leukemia with t(15;17)(q22;q12); PML-RARAb
 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 (megakaryoblastic) with t(1;22)(p13;q13); RBM15-MKL1
 Provisional entity: AML with mutated NPM1
 Provisional entity: AML with mutated CEBPA
AML with myelodysplasia-related changes
Therapy-related myeloid neoplasms
AML not otherwise specified
 AML with minimal differentiation
 AML without maturation
 AML with maturation
 Acute myelomonocytic leukemia
 Acute monoblastic and monocytic leukemia
 Acute erythroid leukemia
 Acute megakaryoblastic leukemia
 Acute basophilic leukemia
 Acute panmyelosis with myelofibrosis
Myeloid sarcoma
Myeloid proliferations related to Down syndrome
 Transient abnormal myelopoiesis
 Myeloid leukemia associated with Down syndrome
Blastic plasmacytoid dendritic cell neoplasm
Acute leukemia of ambiguous lineage
 Acute undifferentiated leukemia
 Mixed phenotype acute leukemia with t(9;22)(q34;q11,20); BCR-ABL11
 Mixed phenotype acute leukemia with t(v;11q23); MLL rearranged
 Mixed phenotype acute leukemia, B/myeloid, NOS
 Mixed phenotype acute leukemia, T/myeloid, NOS
 Provisional entity: Natural killer (NK)-cell lymphoblastic leukemia/lymphoma
French-American-British (FAB) classificationc
 MO: Minimally differentiated leukemia
 Ml: Myeloblastic leukemia without maturation
 M2: Myeloblastic leukemia with maturation
 M3: Hypergranular promyelocytic leukemia
 M4: Myelomonocytic leukemia
 M4Eo: Variant: Increase in abnormal marrow eosinophils
 M5: Monocytic leukemia
 M6: Erythroleukemia (DiGuglielmo’s disease)
 M7: Megakaryoblastic leukemia
aData from Swerdlow SH et al (eds): World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, 4th edition update, IARC Press, 2017.
bDiagnosis is AML regardless of blast count.
cData from Bennett JM et al: Proposed revised criteria for the classification of acute myeloid leukemia. Ann Intern Med 103:620, 1985.
Abbreviation: AML, acute myeloid leukemia.

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