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Key Points

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  • Disease summary:

    • Acute myeloid leukemia (AML) is a malignant disease originating from a hematopoietic cell that has acquired self-renewal properties. Hundreds of genetic aberrations have been described in AML cells, and recent evidence suggests that on average 13 genetic aberrations are present in AML cells.

    • Patients usually present with signs of anemia, infection, or bleeding.

    • The diagnosis is made if greater than or equal to 20 myeloid blasts are present in peripheral blood or bone marrow.

    • Conventional cytogenetics and molecular screening for fusion proteins PML-RARα, RUNX1-RUNX1T1, CBFB-MYH11, and for mutations of NPM1, CEBPA, and FLT3 should be obtained at diagnosis.

    • Intensive chemotherapy should be given to all eligible patients consisting of cytarabine and an anthracycline.

    • Consolidation treatment consists of high-dose cytarabine or allogeneic hematopoietic stem cell transplantation depending on prognostic factors.

    • Acute promyelocytic leukemia (APL) is treated differently than other AML patients (including all-trans retinoic acid [ATRA] and an anthracycline) and has a good prognosis.

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  • Differential diagnosis:

    • Includes myelodysplastic syndromes (MDSs), aplastic anemia, other leukemias, or myeloproliferative neoplasms.

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  • Monogenic forms:

    • No monogenic form of AML is known. However, AML can be recapitulated in the xenotransplant model by overexpression of the fusion gene MLL-AF9 and MLL-ENL in human cord blood cells.

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  • Family history:

    • AML is considered as an acquired disease with no increased risk for family members. However, there are rare familial cases of AML in whom germline mutations in RUNX1, CEBPA, and GATA2 have been found; 20% to 60% of carriers of these mutations develop myeloid malignancies.

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  • Twin studies:

    • Twin studies showed a high rate of concordance of AML between identical twins. However, the risk to develop AML for the twin of an AML patient is similar as in the normal population after the age of 6.

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  • Environmental factors:

    • Exposure to benzene, radiation, and chemotherapy (topoisomerase II inhibitors, alkylating agents) are known risk factors for AML.

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  • Genome-wide associations:

    • Three single-nucleotide polymorphisms (SNPs) have been identified to confer susceptibility to therapy-related AML (rs1394384, rs1381392, and rs1199098). They have not been prospectively tested to guide management of patients treated with chemotherapy.

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  • Pharmacogenomics:

    • SNPs in activating and inactivating enzymes of cytarabine have been shown to affect treatment toxicity and outcome, but are not routinely evaluated. Cytarabine dose is currently not adapted to the genotype of its metabolizing enzymes.

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Diagnostic Criteria and Clinical Characteristics

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Diagnostic evaluation should include.

  • Differential blood count.

  • Wright-Giemsa stained blood or bone marrow smears evaluated by light microscopy to verify the presence of greater than or equal to 20% myeloid blasts.

  • Myeloid lineage of blast cells is confirmed by cytochemical stains such as myeloperoxidase, Sudan black B (myeloid) or nonspecific esterase (monocytic), and/or by immunophenotyping for hematopoietic progenitor cells (CD34, HLA-DR, CD117), myeloid (MPO, CD13, CD33), monocytic (CD14, CD64), erythroid (CD71, glycophorin A), or megakaryoblastic (CD41, CD61) cell surface ...

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