The Molecular Biology of Acute Myeloid Leukemia

Radich, Jerald P.

doi:10.1002/9781444394016.ch6

Cited by 1 publication

(1 citation statement)

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“…AML is the most common acute leukaemia affecting adults, and its incidence increases with age [ 19 ]. However, AML is a heterogeneous disease driven by a wide variety of genetic lesions [ 20 ]. In patients fit enough for conventional intensive cytotoxic chemotherapy, the treatment destroys actively cycling leukaemic cells and initial remission rates are high.…”

Section: Acute Myeloid Leukaemiamentioning

confidence: 99%

Oxidative Stress Responses and NRF2 in Human Leukaemia

Abdul‐Aziz

MacEwan

Bowles

et al. 2015

Oxidative Medicine and Cellular Longevity

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Oxidative stress as a result of elevated levels of reactive oxygen species (ROS) has been observed in almost all cancers, including leukaemia, where they contribute to disease development and progression. However, cancer cells also express increased levels of antioxidant proteins which detoxify ROS. This includes glutathione, the major antioxidant in human cells, which has recently been identified to have dysregulated metabolism in human leukaemia. This suggests that critical balance of intracellular ROS levels is required for cancer cell function, growth, and survival. Nuclear factor (erythroid-derived 2)-like 2 (NRF2) transcription factor plays a dual role in cancer. Primarily, NRF2 is a transcription factor functioning to protect nonmalignant cells from malignant transformation and oxidative stress through transcriptional activation of detoxifying and antioxidant enzymes. However, once malignant transformation has occurred within a cell, NRF2 functions to protect the tumour from oxidative stress and chemotherapy-induced cytotoxicity. Moreover, inhibition of the NRF2 oxidative stress pathway in leukaemia cells renders them more sensitive to cytotoxic chemotherapy. Our improved understanding of NRF2 biology in human leukaemia may permit mechanisms by which we could potentially improve future cancer therapies. This review highlights the mechanisms by which leukaemic cells exploit the NRF2/ROS response to promote their growth and survival.

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Section: Acute Myeloid Leukaemiamentioning

confidence: 99%