Challenges in Treating Older Patients with Acute Myeloid Leukemia

Whereas in younger patients diagnosed with acute myeloid leukemia (AML) treatment is straightforward and the goal is cure, the optimal treatment decision for older adults remains highly controversial. Physicians need to determine whether palliation, “something” beyond palliation, intensive therapy, or an investigational therapy is the most appropriate treatment option. This requires understanding of the biology and risk profile of the AML, clinical judgment in evaluating the functional status of the patient, communication skills in understanding the patient's wishes and social background, and medical expertise in available therapies. The physician has to accurately inform the patient about (a) the unique biological considerations of his leukemia and his prognosis; (b) the risks and benefits of all available treatment options; (c) novel therapeutic approaches and how the patient can get access to these treatments. Last but not least, he has to recommend a treatment. This paper tries to discuss each of these issues

BCL-2 Inhibition Targets Oxidative Phosphorylation and Selectively Eradicates Quiescent Human Leukemia Stem Cells

SummaryMost forms of chemotherapy employ mechanisms involving induction of oxidative stress, a strategy that can be effective due to the elevated oxidative state commonly observed in cancer cells. However, recent studies have shown that relative redox levels in primary tumors can be heterogeneous, suggesting that regimens dependent on differential oxidative state may not be uniformly effective. To investigate this issue in hematological malignancies, we evaluated mechanisms controlling oxidative state in primary specimens derived from acute myelogenous leukemia (AML) patients. Our studies demonstrate three striking findings. First, the majority of functionally defined leukemia stem cells (LSCs) are characterized by relatively low levels of reactive oxygen species (termed “ROS-low”). Second, ROS-low LSCs aberrantly overexpress BCL-2. Third, BCL-2 inhibition reduced oxidative phosphorylation and selectively eradicated quiescent LSCs. Based on these findings, we propose a model wherein the unique physiology of ROS-low LSCs provides an opportunity for selective targeting via disruption of BCL-2-dependent oxidative phosphorylation

Horizontal DNA and mRNA transfer between donor and recipient cells after allogeneic hematopoietic cell transplantation?

Allogeneic hematopoietic cell transplantation in humans results in true biological chimeras. There is now accumulating evidence that besides Graft versus Host Disease (GvHD), there are also other consequences in the co-existence of two genetically distinct populations in the transplant recipient. First, epithelial cells with donorderived genotype emerge. Second, epithelial tissues of the host acquire genomic alterations. The current review discusses existing data on these recently discovered phenomena and focuses on horizontal gene transfer between donor and recipient cells as a possible mechanism explaining and linking these phenomena