Abstract: This invention provides, as a therapeutic method for eradication of neoplastic diseases of the blood with poor diagnosis, a cell co-expressing a chimeric antigen receptor (CAR) protein and a CXCL12 receptor protein on the cell membrane, and an agent and a pharmaceutical composition having anti-tumor activity, which comprises such cell.

Abstract: This invention relates to compounds, compositions and methods for treating leukemia, such as acute myeloid leukemia, in subjects where one or more mutations in FLT3 kinase are present.

Abstract: The present invention provides a therapeutic composition for intractable leukemia comprising a drug (a) and a drug (b), wherein the drug (a) is a compound represented by the following formula (I), a salt thereof, or a prodrug thereof: wherein, Ar1 is a substituted or unsubstituted arylene group; Ar2 is a substituted or unsubstituted aryl group or a substituted or unsubstituted aralkyl group; L is an oxygen atom, —NHCO—, or —CONH—; X1 is CH; X2 and X3 are CH and a nitrogen atom, respectively; Y is an ethylene group; m is 0; and Z1 and Z2 form a substituted or unsubstituted monocyclic heterocyclic group comprising X3 and having two nitrogen atoms as ring members, and the drug (b) is a steroidal anti-inflammatory drug; and relates to a therapy for intractable leukemia.

Abstract: The present invention provides a therapeutic composition for intractable leukemia comprising a drug (a) and a drug (b), wherein the drug (a) is a compound represented by the following formula (I), a salt thereof, or a prodrug thereof: wherein, Ar1 is a substituted or unsubstituted arylene group; Ar2 is a substituted or unsubstituted aryl group or a substituted or unsubstituted aralkyl group; L is an oxygen atom, —NHCO—, or —CONH—; X1 is CH; X2 and X3 are CH and a nitrogen atom, respectively; Y is an ethylene group; m is 0; and Z1 and Z2 form a substituted or unsubstituted monocyclic heterocyclic group comprising X3 and having two nitrogen atoms as ring members, and the drug (b) is a steroidal anti-inflammatory drug; and relates to a therapy for intractable leukemia.

Abstract: This invention relates to an agent for treating or inhibiting recurrence of acute myeloid leukemia and an agent for inhibiting growth of leukemia stem cells comprising a compound represented by formula (I) or a salt thereof: wherein Ar1 and Ar2 each represent aryl or heteroaryl; L represents O, S, NH, NHCO, or CONH; X represents CH or N; Y represents C1-3-alkylene; Z1 represents hydrogen, C1-6-alkyl, amino-C1-6-alkyl, C1-6-alkylamino-C1-6-alkyl, di(C1-6-alkyl)amino-C1-6-alkyl, hydroxy-C1-6-alkyl, C1-6-alkoxy-C1-6-alkyl, or carboxy-C1-6-alkyl; and Z2 represents C1-6-alkyl, amino-C1-6-alkyl, C1-6-alkylamino-C1-6-alkyl, di(C1-6-alkyl)amino-C1-6-alkyl, hydroxy-C1-6-alkyl, C1-6-alkoxy-C1-6-alkyl, or carboxy-C1-6-alkyl, Z1 and Z2 may, together with adjacent nitrogen, form a heterocyclic group containing as a ring member one or more hetero atoms, in addition to the nitrogen adjacent to Z1 and Z2.

Abstract: The invention relates to a method of selectively expanding human leukemic cells in a non-adult NOD/SCID/IL2rgnull mouse by transplanting a substance containing a leukemic stem cell derived from a human acute myelogenous leukemia patient to the mouse. In addition, the invention relates to screening for a medicament capable of eradicating leukemic stem cell (LSC), consideration of treatment methods suitable for individual patients, identification of a differentially expressed gene and the like, using a mouse with expanded human leukemic cells.

Abstract: This invention relates to an agent for treating or inhibiting recurrence of acute myeloid leukemia and an agent for inhibiting growth of leukemia stem cells comprising a compound represented by formula (I) or a salt thereof: wherein Ar1 and Ar2 each represent aryl or heteroaryl; L represents O, S, NH, NHCO, or CONH; X represents CH or N; Y represents C1-3-alkylene; Z1 represents hydrogen, C1-6-alkyl, amino-C1-6-alkyl, C1-6-alkylamino-C1-6-alkyl, di(C1-6-alkyl)amino-C1-6-alkyl, hydroxy-C1-6-alkyl, C1-6-alkoxy-C1-6-alkyl, or carboxy-C1-6-alkyl; and Z2 represents C1-6-alkyl, amino-C1-6-alkyl, C1-6-alkylamino-C1-6-alkyl, di(C1-6-alkyl)amino-C1-6-alkyl, hydroxy-C1-6-alkyl, C1-6-alkoxy-C1-6-alkyl, or carboxy-C1-6-alkyl, Z1 and Z2 may, together with adjacent nitrogen, form a heterocyclic group containing as a ring member one or more hetero atoms, in addition to the nitrogen adjacent to Z1 and Z2.

Abstract: The invention provides a test method for predicting the initial onset or a recurrence of acute myeloid leukemia (AML) comprising (1) measuring the expression level of human leukemic stem cell (LSC) marker genes in a biological sample collected from a subject for a transcription product or translation product of the gene as an analyte and (2) comparing the expression level with a reference value; an LSC-targeting therapeutic agent for AML capable of suppressing the expression of a gene selected from among LSC marker genes or a substance capable of suppressing the activity of a translation product of the gene; a method for producing a sample containing hematopoietic cells for autologous transplantation or allogeneic transplantation for AML patients, comprising obtaining an LSC-purged sample with at least 1 kind of LSC marker as an index; and a method of preventing or treating AML.

Abstract: The present invention provides a drug capable of initiating the progression of the cell cycle of leukemia stem cells to overcome the resistance of the leukemia stem cells to cell cycle-dependent chemotherapeutic agents, and a drug for suppressing recurrence of leukemia containing the same, and the like, an agent containing G-CSF, wherein the agent is for inducing the progression of the cell cycle of leukemia stem cells, a drug for suppressing recurrence of leukemia containing a combination of G-CSF and a cell cycle-dependent antitumor agent, and the like.

Abstract: The invention provides a test method for predicting the initial onset or a recurrence of acute myeloid leukemia (AML) comprising (1) measuring the expression level of human leukemic stem cell (LSC) marker genes in a biological sample collected from a subject for a transcription product or translation product of the gene as an analyte and (2) comparing the expression level with a reference value; an LSC-targeting therapeutic agent for AML capable of suppressing the expression of a gene selected from among LSC marker genes or a substance capable of suppressing the activity of a translation product of the gene; a method for producing a sample containing hematopoietic cells for autologous transplantation or allogeneic transplantation for AML patients comprising obtaining an LSC-purged sample with at least 1 kind of LSC marker as an index; and a method of preventing or treating AML.

Abstract: The invention relates to a method of selectively expanding human leukemic cells in a non-adult NOD/SCID/IL2rgnull mouse by transplanting a substance containing a leukemic stem cell derived from a human acute myelogenous leukemia patient to the mouse. In addition, the invention relates to screening for a medicament capable of eradicating leukemic stem cell (LSC), consideration of treatment methods suitable for individual patients, identification of a differentially expressed gene and the like, using a mouse with expanded human leukemic cells.

Abstract: The invention generally features methods and compositions for enhancing stem cell function. In particular, the invention provides therapeutic or prophylactic methods that can increase survival, growth or proliferation during blood and/or stem cell transplant and protect stem cells in settings of injury.