Genetic profiling in acute myeloid leukaemia ─ where are we and what is its role in patient management

Abstract

SummaryGenetic profiling in acute myeloid leukaemia (AML) is a moving target. Only 4 years ago, AML was re-classified, based on karyotypic abnormalities. However, numerous important new mutations and other genetic abnormalities that were not considered in this classification have been identified. Current cytogenetic-based classification is limited by the substantial number of intermediate-risk patients in whom the preferred therapy is debatable. In addition, the majority of AML patients co-express multiple mutations and cannot be easily categorized into predefined homogenous groups. The tremendous progress in mass sequencing allows parallel identification of multiple genetic aberrations in large cohorts. Thus, a new concept of genetic profiling has arisen. Genes and proteins biologically interact with each other; therefore, it should not be surprising that mutations in different genes interact. Prognosis is determined by the composition of mutations and aberrations in leukaemic stem cells. As a consequence, clinical decisions no longer rely on scant genetic data and require comprehensive genetic evaluation. Some non-genetic parameters are also important and should be incorporated into the clinical decision algorithm. Genetic interaction-based profiles are challenging and recent studies demonstrate an improvement in prognostic predictions with this model. Thus, genetic profiling is likely to have a major therapeutic impact, at least for intermediate-risk cytogenetics.

Larger Size of Donor Alloreactive NK Cell Repertoire Correlates with Better Response to NK Cell Immunotherapy in Elderly Acute Myeloid Leukemia Patients

“…Many advances in the use of broad-spectrum chemotherapeutic regimens and targeted therapy have improved the CR rate in elderly AML patients (2). However, a significant number of patients who achieve CR after induction/consolidation chemotherapy still harbor a minimal residual disease (MRD), which is often resistant to further chemotherapeutic treatments and eventually leads to relapse and disease progression.…”

Is the D14 bone marrow in acute myeloid leukemia still the gold standard?

“…Some patients are likely to achieve sustained complete response with a single induction cycle, others may benefit from a second subsequent identical cycle, some require prescription of different agents for reinduction, whereas some present with chemorefractory disease and may be subject to nonchemotherapy options only. In the future, AML genetics might become the key for patient assignment to different therapies, but currently there are no data to support the modification of the traditional 3 þ 7 regimen on a personal basis [38,39]. It seems that in the near future, early bone marrow evaluation during induction will remain the best tool for personalizing therapy.…”

Genetic Stratification in Myeloid Diseases: From Risk Assessment to Clinical Decision Support Tool

“…This is particularly significant for acute leukemia, where clinical decisions sometimes depend on the presence or absence of specific mutations 78. The development of next-generation sequencing (NGS) techniques allows parallel quantitative sequencing of large numbers of genes at an affordable price.…”