General AML,   NPM1

A personalized approach for Acute Myeloid Leukemia: biologic, prognostic and therapeutic insights

Khaled et al. reviewed the diagnosis and treatment of Acute Myeloid Leukemia (AML) to provide insights into the emerging novel biomarkers, new molecular approaches and therapeutic agents that are anticipated to be useful for the implementation of personalized medicine in AML. This review has implications for the management of patients with the most unmet needs; older patients and patients with high-risk disease. Their findings were published in Oncology (Williston Park) in April 2016.1

Epigenetic modulators

Hypomethylating agents (HMAs), including 5-azacytidine or decitabine, may be an effective approach in older patients. The effectiveness of these agents was observed in two large randomized trials. Also of note are the results of a landmark 10-day regimen of decitabine, 20mg/m2, in previously untreated older AML patients which demonstrated a 47% complete remission (CR) rate and a 64% overall response (OR) rate.

NPM1 mutations

Nucleophosmin (NPM) is a nucleolar phosphoprotein that normally shuttles between the nucleus and the cytoplasm to maintain cellular processes. Frameshift mutations at the C-terminus of this protein are relatively common in cytogenic-normal (CN-AML) patients (occurring in 45% to 60% of this subset). In older CN-AML patients treated with intensive induction chemotherapy, NPM1 mutations predict for excellent disease response and better survival.

Immunotherapeutic agents

SGN-CD33A, a humanized CD33 antibody conjugated to a pyrrolobenzodiazepine (PBD), has shown promising results in AML patients. Early results from phase I clinical trials have recently been presented. In one trial of SGN-CD33A monotherapy in patients who had CD33-positive AML in relapse or who had declined intensive induction chemotherapy, a dose of 40μg/kg led to a 60% OR rate in treatment-naïve patients.


In summary, in order to improve outcomes in AML patients, the challenge is how to match molecular and clinical information with emerging compounds in order to select the best treatment for individual patients. The success of personalized approaches in AML is likely to depend on the ability to readily attain molecular information and improve patient access to new drugs.


Acute myeloid leukemia (AML) is a biologically complex and molecularly and clinically heterogeneous disease, and its incidence is increasing as the population ages. Unfortunately, currently used “one-size-fits-all” chemotherapy regimens result in cure for only a minority of patients. Although progress has been made in identifying subsets of patients who require chemotherapy alone as compared with those who require initial chemotherapy followed by allogeneic stem cell transplantation to maximize the chance for cure clinical and cytogenetic prognosticators are not sufficiently accurate for such a risk-adapted stratification approach. New molecular technologies have allowed for in-depth molecular analyses of AML patients. These studies have revealed novel mutations, epigenetic changes, and/or aberrant expression levels of protein-coding and noncoding genes involved in leukemogenesis. These molecular aberrations are now being increasingly used not only to select risk-adapted treatment strategies, but also to incorporate newer molecularly targeted agents into conventional chemotherapy and/or transplant treatments. The hope is that this approach will lead to a better selection of “personalized” treatments for individual patients at diagnosis, the ability to assess these treatments in real time, and the ability, if necessary, to modify these therapies utilizing molecular endpoints for guidance regarding their antileukemic activity. We review here the state of the art of diagnosis and treatment of AML and provide insights into the emerging novel biomarkers and therapeutic agents that are anticipated to be useful for the implementation of personalized medicine in AML.

  1. Khaled S, et al. Acute Myeloid Leukemia: Biologic, Prognostic, and Therapeutic Insights. Oncology (Williston Park). 2016 Apr; 30(4): 318–329.
  2. Jonas BA and Medeiros BC. Individualizing therapeutic strategies in Acute Myeloid Leukemia: moving beyond the ‘one-size-fits-all’ Oncology (Williston Park). 2016 Apr; 30(4): 330–333.