cml Biology for the Clinician in 2011: Six Impossible Things to Believe before Breakfast on the Way to Cure

Chronic myeloid leukemia (cml) is a model disease in oncology: it is the first human cancer linked to a distinct chromosomal abnormality, ultimately causing constitutive overactivity of a known oncogenic tyrosine kinase that represents a drug target. The introduction of the tyrosine kinase inhibitor imatinib into clinical practice has far exceeded expectations and resurrected hope that the fundamental insights from the “war on cancer” can lead to significant therapeutic advances. Nevertheless, the current perception among clinicians is that imatinib and its newer more potent cousins offer superb long-term disease control for most patients, but that cure without transplantation has remained elusive. However, several important laboratory-based observations over the last few years have changed those perceptions. Several of those developments are discussed here, including direct manipulation of the apoptosis pathway in cancer cells and prevention of disease progression with the use of antioxidants. Intriguing results from a French study indicate that, if disease progression is halted, a small but significant group of patients may be able to stop imatinib therapy without disease recurrence. And for patients whose disease, because of resistant stem cells, needs a more direct attack than tyrosine kinase inhibitors alone, several approaches investigated in laboratory and animal models seem promising, and some are ripe for clinical testing, including inhibitors of Smoothened and 5-lipoxygenase, and suppression of autophagy. Thus, there is realistic hope that true cure of cml, without transplantation, may be a feasible goal in the near future.