3 - Discussion:
Identification of targetable lesions in AML provides clinicians with novel treatment options to improve clinical outcomes for patients who respond poorly to current conventional chemotherapy, such as patients with Monosomy 7 AML. With ongoing discovery efforts and further interrogation of large patient repositories, we hope to identify additional novel targets, particularly for patients with rare subtypes of AML.
Here, we demonstrate that newly discovered ALKfus in Mono7 AML leads to a functional ALK protein with the ability to transform cells and induce a proliferative advantage in a cytokine-independent manner. We show cells harboring the ALKfus to be susceptible to the ALK inhibitor crizotinib, inducing tumor cell death in the context of AML in vitro modeling systems. We hypothesize treatment with newer generations of ALK-inhibitors will result in more robust tumor cell killing and warrants additional evaluation for exploration. Additionally, to evaluate the preclinical efficacy of treating ALKfusAML with ALK-inhibitors, such as crizotinib, future in vivoexperiments should be performed. The data presented here provide rationale for ongoing exploration of crizotinib as an effective therapeutic option for these high-risk patients with Monosomy7 AML.