Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.

Input: Consider Input: The translocation (9;22) gives rise to the p190(Bcr-Abl) and p210(Bcr-Abl) tyrosine kinase proteins, considered sufficient for leukemic transformation. Philadelphia-positive (Ph(+)) acute leukemia patients failing to respond to initial induction therapy have a poor prognosis with few effective treatment options. Imatinib is an orally administered, potent inhibitor of the Bcr-Abl tyrosine kinase. We conducted a clinical trial in 56 patients with relapsed or refractory Ph(+) acute lymphoblastic leukemia (ALL; 48 patients) or chronic myelogenous leukemia in lymphoid blast crisis (LyBC; 8 patients). Imatinib was given once daily at 400 mg or 600 mg. Imatinib induced complete hematologic responses (CHRs) and complete marrow responses (marrow-CRs) in 29% of ALL patients (CHR, 19%; marrow-CR, 10%), which were sustained for at least 4 weeks in 6% of patients. Median estimated time to progression and overall survival for ALL patients were 2.2 and 4.9 months, respectively. CHRs were reported for 3 (38%) of the patients with LyBC (one sustained CHR). Grade 3 or 4 treatment-related nonhematologic toxicity was reported for 9% of patients; none of the patients discontinued therapy because of nonhematologic adverse reactions. Grade 4 neutropenia and thrombocytopenia occurred in 54% and 27% of patients, respectively. Imatinib therapy resulted in a clinically relevant hematologic response rate in relapsed or refractory Ph(+) acute lymphoid leukemia patients, but development of resistance and subsequent disease progression were rapid. Further studies are warranted to test the effects of imatinib in combination with other agents and to define the mechanisms of resistance to imatinib.

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


Input: Consider Input: In chronic lymphocytic leukemia (CLL) signals from the B cell receptor (BCR) play a major role in disease development and progression. In this light, new therapies that specifically target signaling molecules downstream of the BCR continue to be developed. While first studies on the selective small molecule inhibitor of Bruton's tyrosine kinase (Btk), Ibrutinib (PCI-32765), demonstrated that Btk inhibition sensitizes CLL cells to apoptosis and alters their migratory behavior, these studies however did not address whether Btk-mediated signaling is involved in the process of CLL leukemogenesis. To investigate the requirement of Btk signaling for CLL development, we modulated Btk expression in the IgH.ET CLL mouse model, which is based on sporadic expression of the simian oncovirus SV40 T-antigen in mature B cells. To this end, we crossed IgH.ET mice on a Btk-deficient background or introduced a human Btk transgene (CD19-hBtk). Here we show that Btk deficiency fully abrogates CLL formation in IgH.ET mice, and that leukemias formed in Btk haplo-insufficient mice selectively expressed the wild-type Btk allele on their active X chromosome. Conversely, Btk overexpression accelerated CLL onset, increased mortality, and was associated with selection of non-stereotypical BCRs into CLL clones. Taken together, these data show that Btk expression represents an absolute prerequisite for CLL development and that Btk mediated signaling enhances leukemogenesis in mice. We therefore conclude that in CLL Btk expression levels set the threshold for malignant transformation.

Output: What is the name of Bruton's tyrosine kinase inhibitor that can be used for treatment of chronic lymphocytic leukemia?


Input: Consider Input: DNA is the material that makes up our chromosomes and stores our genetic information. When you build a house, you need a blueprint, a set of instructions that tells you how to build. The DNA is like the blueprint for living organisms. The genetic information is a set of instructions that tell your cells what to do. DNA is an abbreviation for deoxyribonucleic acid. As you may recall, nucleic acids are a type of macromolecule that store information. The deoxyribo part of the name refers to the name of the sugar that is contained in DNA, deoxyribose. DNA may provide the instructions to make up all living things, but it is actually a very simple molecule. DNA is made of a very long chain of nucleotides. In fact, in you, the smallest DNA molecule has well over 20 million nucleotides. Nucleotides are composed of three main parts: 1. a phosphate group. 2. a 5-carbon sugar (deoxyribose in DNA). 3. a nitrogen-containing base. The only difference between each nucleotide is the identity of the base. There are only four possible bases that make up each DNA nucleotide: adenine (A), guanine (G), thymine (T), and cytosine (C). The various sequences of the four nucleotide bases make up the genetic code of your cells. It may seem strange that there are only four letters in the alphabet of DNA. But since your chromosomes contain millions of nucleotides, there are many, many different combinations possible with those four letters. But how do all these pieces fit together? James Watson and Francis Crick won the Nobel Prize in 1962 for piecing together the structure of DNA. Together with the work of Rosalind Franklin and Maurice Wilkins, they determined that DNA is made of two strands of nucleotides formed into a double helix, or a two-stranded spiral, with the sugar and phosphate groups on the outside, and the paired bases connecting the two strands on the inside of the helix (Figure 1.1). The bases in DNA do not pair randomly. When Erwin Chargaff looked closely at the bases in DNA, he noticed that the percentage of adenine (A) in the DNA always equaled the percentage of thymine (T), and the percentage of guanine (G) always equaled the percentage of cytosine (C). Watson and Cricks model explained this result by suggesting that A always pairs with T, and G always pairs with C in the DNA helix. Therefore A and T, and G and C, are "complementary bases," or bases that always pair together, known as a base-pair. The base-pairing rules state that A will always bind to T, and G will always bind to C (Figure 1.2). For example, if one DNA strand reads ATGCCAGT, the other strand will be made up of the complementary bases: TACGGTCA. Hydrogen bonds hold the complementary bases together, with two bonds forming between an A and a T, and three bonds between a G and a C. The chemical structure of DNA includes a chain of nucleotides consisting of a 5- carbon sugar, a phosphate group, and a nitrogen base. Notice how the sugar and phosphate group form the backbone of DNA (strands highlighted in pink), with the hydrogen bonds between the bases joining the two strands.


Output: who determined the percentage of adenine (a) in the dna always equaled the percentage of thymine (t), and the percentage of guanine (g) always equaled the percentage of cytosine (c).