Childhood acute myeloid leukaemia

Abstract

Although acute myeloid leukaemia (AML) has long been recognized for its morphological and cytogenetic heterogeneity, recent high-resolution genomic profiling has demonstrated a complexity even greater than previously imagined. This complexity can be seen in the number and diversity of genetic alterations, epigenetic modifications, and characteristics of the leukaemic stem cells. The broad range of abnormalities across different AML subtypes suggests that improvements in clinical outcome will require the development of targeted therapies for each subtype of disease and the design of novel clinical trials to test these strategies. It is highly unlikely that further gains in long-term survival rates will be possible by mere intensification of conventional chemotherapy. In this review, we summarize recent studies that provide new insight into the genetics and biology of AML, discuss risk stratification and therapy for this disease, and profile some of the therapeutic agents currently under investigation.

Figure 1. Overall survival of patients who were less than 20 years of age and diagnosed with AML during the time periods indicated

The data were obtained from www.seer.cancer.gov/popdata.

Figure 2. Approximate frequencies of recurrent genetic lesions in childhood AML

Frequencies are estimated from (Pui et al, 2011; Meshinchi et al, 2006a; Staffas et al, 2011; Harrison et al, 2010; Ho et al, 2009; Brown et al, 2007; Hollink et al, 2009a; Balgobind et al, 2009; Hollink et al, 2009b; Andersson et al, 2011). ALM, activation loop mutation; ITD, internal tandem duplication; mut, mutation; wt, wild-type