Acute Myeloid Leukemia
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- Acute myeloid leukemia (AML) results from a block in differentiation and unregulated proliferation of myeloid progenitor cells.
- AML is classified according to the World Health Organization (WHO) classification (2008).
- Formerly classified by French-American-British (FAB) classification
- WHO classification is based on genetic alterations, whereas FAB is based on morphology.
- AML is the seventh most common pediatric malignancy.
- Leukemia that occurs in first 4 weeks of life is usually AML.
- Ratio of AML to acute lymphoblastic leukemia (ALL) throughout childhood is 1:5.
- Boys and girls are equally affected.
- Rates are highest in Asian and Pacific Islanders followed by Hispanics, Caucasians, and African Americans.
- AML incidence peaks in infants <1 year of age and again in children 10 to 14 years of age.
- Around 500 children per year in the United States
- 20–30% of pediatric blast cells have normal karyotype versus 40–50% in adults.
- 60% of abnormal karyotypes fall into known subgroups.
- Translocations or duplications of the MLL gene at 11q23 or monosomy 7 carry a poor prognosis.
- These genetic abnormalities are found in many cases of therapy-induced AML.
- FLT3-ITD with high allelic ratio, a drug targetable lesion, has also been shown to carry a poor prognosis.
- Translocations t(8;21), t(15;17), and inv(16), as well as NPM and CEPBα mutations carry a good prognosis.
- AML associated with Down syndrome has an excellent prognosis.
- Certain congenital syndromes that carry an increased risk of AML:
- Fanconi anemia
- Bloom syndrome
- Neurofibromatosis type 1
- Down syndrome
- Severe congenital anemia (i.e., Kostmann disease treated with granulocyte colony-stimulating factor)
- Diamond-Blackfan anemia
- Paroxysmal nocturnal hemoglobinemia
- Li-Fraumeni syndrome
- Shwachman-Diamond syndrome
- Dyskeratosis congenita
- Noonan syndrome (RASopathies)
- Principal defect is a block in the differentiation of primitive myeloid precursor cells.
- Two mechanisms predominate:
- Defect at the level of transcriptional activation
- Defects in the signaling pathway of hematopoietic growth factors. For example, the proto-oncogene Ras is mutated in up to 1/3 of patients with AML.
- Exact cause unknown in most cases
- Acquired risk factors include the following:
- Exposure to benzene
- Exposure to ionizing radiation
- Therapy induced, from chemotherapy for a prior malignancy
- Alkylating agents such as cyclophosphamide, nitrogen mustard, chlorambucil, and melphalan (typically presents several years after therapy)
- Epipodophyllotoxins such as VP16, VM26 (typically occurs within 2 years after therapy and is characterized by rearrangements involving 11q23)