Abstract: Methods of treating acute myeloid leukemia, chronic lymphocytic leukemia and myeloproliferative neoplasms that involve the administration of combinations of small molecule compounds are disclosed.

Abstract: Methods of treating acute myeloid leukemia, chronic lymphocytic leukemia and myeloproliferative neoplasms that involve the administration of combinations of small molecule compounds are disclosed.

Abstract: Disclosed herein are methods and kits used in treating a cancer characterized by aberrant activity of CSF3R. These methods involve detecting a mutation in exon 14 of CSF3R such as a mutation of T615 or T618 and treating the subject with a JAK inhibitor and/or detecting a mutation in exon 17 of CSF3R and treating with dasatinib or tyrosine kinase inhibitor with one or more targets in common with dasatinib.

Abstract: Disclosed herein are methods and kits used in treating a cancer characterized by aberrant activity of CSF3R. These methods involve detecting a mutation in exon 14 of CSF3R such as a mutation of T615 or T618 and treating the subject with a JAK inhibitor and/or detecting a mutation in exon 17 of CSF3R and treating with dasatinib or tyrosine kinase inhibitor with one or more targets in common with dasatinib.

Abstract: Disclosed herein are methods and kits used in treating a cancer characterized by aberrant activity of CSF3R. These methods involve detecting a mutation in exon 14 of CSF3R such as a mutation of T615 or T618 and treating the subject with a JAK inhibitor and/or detecting a mutation in exon 17 of CSF3R and treating with dasatinib or tyrosine kinase inhibitor with one or more targets in common with dasatinib.

Abstract: In accordance with the invention, a novel activating mutation (alanine 572 to valine) in JAK3 kinase has been discovered in human acute myelogenous leukemia (AML). The mutant JAK3 kinase was confirmed to drive the proliferation and survival of acute megakaryoblastic leukemia (AML-M7). The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant JAK3 kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the mutant polypeptides. The disclosed identification of this new mutant protein and enables new methods for determining the presence of mutant JAK3 kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the mutant proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

Abstract: In accordance with the invention, a novel gene translocation, (3p21, 5q33), in human myelogenous leukemia (AML) that results in a fusion protein combining part of RNA Binding Protein-6 (RBM6) with Macrophage Colony Stimulating Factor-1 Receptor (CSF1R) kinase has now been identified. The RBM6-CSF1R fusion protein and truncated CSF1R kinase itself, which both retain CSF1R tyrosine kinase activity, were confirmed to drive the proliferation and survival of acute megakaryoblastic leukemia (AML-M7). The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant CSF1R kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides.

Abstract: The present invention relates to isolated polypeptides which comprise an amino acid sequence consisting of a mutated functional Abl kinase domain, said mutated functional kinase domain being resistant to inhibition of its tyrosine kinase activity by N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-(4-methyl-piperazin-1-ylmethyl)-benzamide or a salt thereof, to the use of such polypeptides to screen for compounds which inhibit the tyrosine kinase activity of such polypeptides, to nucleic acid molecules encoding such polypeptides, to recombinant vectors and host cells comprising such nucleic acid molecules and to the use of such nucleic acid molecules in the production of such polypeptides for use in screening for compounds which inhibit the tyrosine kinase activity of such polypeptides.

Abstract: The present invention relates to isolated polypeptides which comprise an amino acid sequence consisting of a mutated functional Abl kinase domain, said mutated functional kinase domain being resistant to inhibition of its tyrosine kinase activity by N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-(4-methyl-piperazin-1-ylmethyl)-benzamide or a salt thereof, to the use of such polypeptides to screen for compounds which inhibit the tyrosine kinase activity of such polypeptides, to nucleic acid molecules encoding such polypeptides, to recombinant vectors and host cells comprising such nucleic acid molecules and to the use of such nucleic acid molecules in the production of such polypeptides for use in screening for compounds which inhibit the tyrosine kinase activity of such polypeptides.

Abstract: The tides which comprise an amino acid sequence consisting of a mutated functional Abl kinase domain, said mutated functional kinase domain being resistant to inhibition of its tyrosine kinase activity by N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-(4-methyl-piperazin-1-ylmethyl)-benzamide or a salt thereof, to the use of such polypeptides to screen for compounds which inhibit they tyrosine kinase activity of such polypeptides, to nucleic acid molecules encoding such polypeptides, to recombinant vectors and host cells comprising such nucleic acid molecules and to the use of such nucleic molecules in the production of such polypeptides for use in screening for compounds which inhibit the tyrosine kinase activity of such polypeptides.

Abstract: The present invention relates to isolated polypeptides which comprise a functional kinase domain comprising the amino acid sequence of the native human Abl kinase domain or an essentially similar sequence thereof in which at least one amino acid selected from Met244, Leu248, Gly250, Glu252, Tyr253, Val256, Glu258, Phe311, Ile313, Phe317, Met318, Met351, Glu355, Glu359, Ile360, His361, Leu370, Asp381, Phe382, His396, Ser417, Glu459 and Phe486 is replaced by another amino acid, said mutated functional kinase domain being resistant to inhibition of its tyrosine kinase activity by N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-(4-methyl-piperazin-1-ylmethyl)-benzamide or a salt thereof, to the use of such polypeptides to screen for compounds which inhibit the tyrosine kinase activity of such polypeptides, to nucleic acid molecules encoding such polypeptides, to recombinant vectors and host cells comprising such nucleic acid molecules and to the use of such nucleic acid molecules in the production of