Distinct subsets can be identified using GEP that correspond to known cytogenetic and molecular abnormalities.
Patients with leukemias that express the progenitor cell antigen CD34 and/or the P-glycoprotein ( Cytogenetic analysis provides some of the strongest prognostic information available, predicting outcome of both remission induction and postremission therapy, as seen in a trial from the Southwest Oncology Group (SWOG) and the Eastern Cooperative Oncology Group (ECOG) (E-3489). Cytogenetic abnormalities that indicate a good prognosis include t(8; 21), inv(16) or t(16;16), and t(15;17). Patients with AML that is characterized by deletions of the long arms or monosomies of chromosomes 5 or 7; by translocations or inversions of chromosome 3, t(6; 9), t(9; 22); or by abnormalities of chromosome 11q23 have particularly poor prognoses with chemotherapy.
This threshold value for blast percentage eliminated the category “refractory anemia with excess blasts in transformation” (RAEB-t) found in the FAB classification of myelodysplastic syndromes (MDS), where RAEB-t is defined by a marrow blast percentage between 20% and 29%.
In the WHO classification, RAEB-t is no longer considered a distinct clinical entity and is instead included within the broader category “AML with multilineage dysplasia” as “AML with multilineage dysplasia following a myelodysplastic syndrome.” Although this lowering of the blast threshold has been met with some criticism, several studies indicate that survival patterns for cases with 20% to 29% blasts are similar to survival patterns for cases with 30% or more blasts in the bone marrow.[5-9] The diagnosis of AML in itself does not represent a therapeutic mandate.
GEP identified several cases of CBF leukemias that were not diagnosed using conventional cytogenetics.[10-12] Next-generation sequencing of AML genomes has identified an average of 13 mutations per case.
Mutated genes include transcription-factor fusions, nucleophosmin-1, tumor-suppressor, DNA-methylation-related, signaling, chromatin-modifying, myeloid transcription-factor, cohesion-complex, and spliceosome-complex. In the following outline and discussion, the older FAB classifications are noted where appropriate.