Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
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Question: Chronic myeloid leukemia (CML) is a progressive and often fatal myeloproliferative neoplasm. The hallmark of CML is an acquired chromosomal translocation known as the Philadelphia chromosome (Ph), which results in the synthesis of the breakpoint cluster region-Abelson murine leukemia (BCR-ABL) fusion oncoprotein, a constitutively active tyrosine kinase. The introduction of imatinib, a tyrosine kinase inhibitor (TKI) that is specific for BCR-ABL, was a major breakthrough in CML therapy. Although most patients respond to first-line imatinib therapy, some experience loss of response (resistance) or require treatment discontinuation because of toxicity (intolerance). For patients with CML, failure on standard-dose imatinib therapy (400 mg daily), imatinib dose escalation (600-800 mg daily) is a second-line option. However, high-dose imatinib is not an appropriate approach for patients who experience drug toxicity, and there remain questions over the durability of responses achieved with this strategy. Alternative second-line options include the TKIs dasatinib and nilotinib. A substantial amount of long-term data for these agents is available. Although both are potent and specific BCR-ABL TKIs, dasatinib and nilotinib exhibit unique pharmacologic profiles and response patterns relative to different patient characteristics, such as disease stage and BCR-ABL mutation status. To optimize therapeutic benefit, clinicians should select treatment based on each patient's historic response, adverse-event tolerance, and risk factors.

Answer: What tyrosine kinase, involved in a Philadelphia- chromosome positive chronic myelogenous leukemia, is the target of Imatinib (Gleevec)?


Question: Everywhere man is altering the balance of nature.He is facilitating the spread of plants and animals into new regions, sometimes deliberately, sometimes unconsciously.He is covering huge areas with new kinds of plants, or with houses, factories, slag-heaps and other products of his civilization.He exterminates some species on a large scale, but favours the multiplication of others.In brief, he has done more in five thousand years to alter the biological aspect of the planet than has nature in five million. Many of these changes which he has brought about have had unforeseen consequences.Who would have thought that the throwing away of a piece of Canadian waterweed would have caused half the waterways of Britain to be blocked for a decade, or that the provision of pot cacti for lonely settlers' wives would have led to Eastern Australian being overrun with forests of Prickly Pear? Who would have prophesied that the cutting down of forests on the Adriatic coasts, or in parts of Central Africa, could have reduced the land to a semidesert, with the very soil washed away from the bare rock? Who would have thought that improved communications would have changed history by the spreading of disease-sleeping sickness into East Africa, measles into Oceania, very possibly malaria into ancient Greece? These are spectacular examples; but examples on a smaller scale are everywhere to be found.We make a nature sanctuary for rare birds, prescribing absolute security for all species; and we may find that some common and hardy kind of bird multiplies beyond measure and ousts the rare kinds in which we were particularly interested.We see, owing to some little change brought about by civilization, the starling spread over the English country-side in hordes.We improve the yielding capacities of our cattle; and find that now they exhaust the pastures which sufficed for less exigent stock.

Answer: What have spread diseases?


Question: The Life Before This is a 1999 Canadian film directed by Jerry Ciccoritti.

Answer:
What is the year that The Life Before This was released?


