The previous classification of AML by French, American, and British (FAB) system (based on AML cells morphology) has been largely replaced with an advanced system (WHO classification system) based on immunophenotype information derived from various cytogenetic tests. Based on the immunophenotypes, the AML is broadly categorized into following types:
- AML with certain genetic abnormalities:
-AML with a translocation between chromosomes 8 and 21
-AML with a translocation or inversion in chromosome 16
-AML with a translocation between chromosomes 9 and 11
-APL with a translocation between chromosomes 15 and 17
-AML with a translocation between chromosomes 6 and 9
-AML with a translocation or inversion in chromosome 3
-AML (megakaryoblastic) with a translocation between chromosomes 1 and 22
- AML with myelodysplasia-related changes
- AML related to previous chemotherapy or radiation
- AML not otherwise specified
-AML with minimal differentiation (M0)
-AML without maturation (M1)
-AML with maturation (M2)
-Acute myelomonocytic leukemia (M4)
-Acute monocytic leukemia (M5)
-Acute erythroid leukemia (M6)
-Acute megakaryoblastic leukemia (M7)
-Acute basophilic leukemia
-Acute panmyelosis with fibrosis
- Myeloid sarcoma (also known as granulocytic sarcoma or chloroma)
- Myeloid proliferations related to Down syndrome
- Undifferentiated and biphenotypic acute leukemias (both lymphocytic and myeloid features are present in such cases)
Each of these types consists of different cytogenetic and molecular characteristics. Analysis of cytogenetic and molecular abnormalities play important role in the diagnosis of the disease and to estimate disease prognosis. Following are certain examples:
1.Chromosome abnormalities: Presence of following abnormalities is generally associated with the favorable outcome: translocation between chromosomes 8 and 21; translocation and between chromosome 15 and 17; and Inversion of chromosome 16.
Similarly, the presence of following cytogenetic abnormalities is generally associated with poor outcome: deletion of part of chromosome 5 or 7; translocation or inversion of chromosome 3; translocation between chromosomes 6 and 9 and between chromosomes 9 and 22; abnormalities of chromosome 11; and complex changes involving several chromosomes.
2.Genetic abnormalities: Poor prognosis is indicated by the presence of a mutation in the FLT3 gene, while a mutation in NPM1 gene (without any other change) and CEBPA gene suggest a better outcome.
3.Cell Surface Protein: Presence of CD34 protein and/or the P-glycoprotein on the surface of leukemia cells generally indicates a worse outcome.
Other prognostic factors which govern the severity of AML include patient’s age, WBC count, CNS involvement, response to induction therapy, prior hematological disorder. With the progress in understanding about the disease and genetic abnormalities involved, immunophenotypic/cytogenetic characterization has become an important parameter for selecting an appropriate treatment approach.
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