Abstract
Acute myeloid leukemia (AML) is a heterogenous disorder that results from a block in the differentiation of hematopoietic progenitor cells along with uncontrolled proliferation. In approximately 60% of cases, specific recurrent chromosomal aberrations can be identified by modern cytogenetic techniques. This cytogenetic information is the single most important tool to classify patients at their initial diagnosis into three prognostic categories: favorable, intermediate, and poor risk. Currently, favorable risk AML patients are usually treated with contemporary chemotherapy while poor risk AML patients receive allogeneic stem cell transplantation if suitable stem cell donors exist. The largest subgroup of AML patients (~40%) have no identifiable cytogenetic abnormalities and are classified as intermediate risk. The optimal therapeutic strategies for these patients are still largely unclear. Recently, it is becoming increasingly evident that it is possible to identify a subgroup of poorer risk patients among those with normal cytogenic AML (NC-AML). Molecular risk stratification for NC-AML patients may be possible due to mutations of NPM1, FLT3, MLL, and CEBPα as well as alterations in expression levels of BAALC, MN1, ERG, and AF1q. Further prospective studies are needed to confirm if poorer risk NC-AML patients have improved clinical outcomes after more aggressive therapy.
Highlights
Acute Myeloid Leukemia (AML) is a broad range of disorders that are all characterized by an arrest of maturation along with uncontrollable proliferation of hematopoietic progenitor cells
The silencing of wild-type mixed lineage leukemia gene (MLL) in blasts positive for MLL-PTD was reversed by DNA methyltransferase and histone deacetylase inhibitors [36]. These findings indicate the potential therapeutic role of the DNA methyltransferase and histone deacetylase inhibitors such as decitabine and valpoic acid in these AML patients
Gene expression and profiling studies have shown that normal cytogenic AML (NC-AML) is very heterogeneous at the molecular level
Summary
Acute Myeloid Leukemia (AML) is a broad range of disorders that are all characterized by an arrest of maturation along with uncontrollable proliferation of hematopoietic progenitor cells. Consistent with the findings in the pediatric AML study, MDS patients with high AF1q expression have an increased hazard ratio of death from MDS and relapse after allogeneic stem cell transplantation with correlation of specific poor cytogenetics These observations led to a hypothesis that elevated AF1q expression might serve an adverse molecular marker for poor prognosis in AML patients with normal cytogenetics. Http://www.jhoonline.org/content/2/1/23 group of the AF1qhigh patients who received allogeneic stem cell transplantation (SCT) had a significant better relapse-free survival compared to patients who received chemotherapy/autologous SCT (p = 0.04) This suggests that high AF1q expression is a poor prognostic marker for adult NC-AML patients and may help direct post-induction treatment strategies. Molecular genetic alterations with prognostic significance have been reported in these patients They include internal tandem duplication of the FLT3 gene, partial tandem duplication of the MLL gene, mutations of the CEBPα and NPM1 genes and aberrant expression of the BAALC, ERG and MN1 genes. MRD monitoring via these molecular markers is not commercially available to the community physician, but these studies provide insight to their future potential in MRD monitoring
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