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Charles Mullighan, MBBS(Hons), MSc, MD, led the multi-institutional study confirming that the cancer has distinct subtypes that are distinguished by the number of chromosomes lost and the submicroscopic genetic alterations they harbor.
Almost all human cells carry DNA condensed into 46 chromosomes, half from each parent. But the major hypodiploid ALL subtypes—low hypodiploid ALL and near haploid ALL—carry significantly fewer. Near haploid ALL has 24 to 31 chromosomes. Low hypodiploid ALL has 32 to 39.
Among the newly discovered mutations in this high-risk leukemia, researchers found virtually all patients with low hypodiploid ALL had mistakes in a gene named TP53 that helps suppress tumor formation. More than one-third of these mutations were inherited. That was the first evidence that low hypodiploid ALL is likely a manifestation of Li-Fraumeni syndrome. The syndrome leaves affected individuals at high risk of developing a variety of cancers and makes them candidates for stepped-up cancer screenings.
Researchers reported that both low hypodiploid and near haploid ALL are sensitive to a family of chemical compounds that block the proliferation of cancer cells by switching off a key pathway in the cells. The group included drugs already used to treat other cancers. Researchers are now testing these and other drugs in additional laboratory models.
Abridged from Promise, Spring 2013