51 results about "Leukemia Stem Cell" patented technology

Disclosed herein are compositions and methods to treat and reduce therapeutic resistance in chronic myelogenous leukemia. Also disclosed herein are methods to generate leukemia stem cell like cells (iLSCs) generated from CML patient-derived iPSCs, and methods for utilizing iLSCs in screens to identify modulators of CML drug resistance and gene targets that underlie CML drug resistance.

The present invention discloses nucleic acids, proteins, and antibodies for SALL4 (including isoforms SALL4A, SALL4B, and SALL4C), a zinc finger transcriptional factor. Further, methods are disclosed which demonstrate that constitutive expression of SALL4 increases leukemogenic potential in cells of model animal systems. Moreover, constitutive expression of select isoforms (e.g., SALL4B) in transgenic mice demonstrate that these animals develop myelodysplastic syndrome (MDS)-like signs and symptoms, including subsequent acute myeloid leukemia (AML), which is transplantable. The disclosure also provides methods for identifying and purifying embryonic stem cells, adult stem cells, cancer stem cells, including leukemia stem cells, methods for identifying substances which bind to and/or modulate SALL4, methods for diagnosing MDS in a subject, and methods of treating a subject presenting MDS, AML and other forms of leukemia.

Methods, compositions, and kits are provided for providing a diagnosis, a prognosis, or a prediction of responsiveness to a therapy for a patient with a hematological malignancy. In practicing the subject methods, the expression level of at least one leukemia stem cell (LSC) genes in a tissue sample is assayed to obtain an LSC expression representation. The LSC expression representation is then employed to determine if an individual has a hematological malignancy, to provide a prognosis to a patient with a hematological malignancy, and/or to provide a prediction of the responsiveness of a patient with a hematological malignancy to a therapy. Also provided are screening methods for identifying novel therapies for patients with a hematological malignancy, and compositions and kits for use in these screening methods.

The invention provides a single-stranded antibody fusion protein in growth factor receptors of human fibroblast cells. The single-stranded antibody fusion protein is an FGFR single-stranded antibody-alkaline polypeptide fusion protein, wherein the FGFR single-stranded antibody is the single-stranded antibody of FGFR1, 2, 3 or 4; and alkaline polypeptide is a polypeptide which comprises 9 to 30 alkaline amino acids. The invention further provides the application of the FGFR single-stranded antibody-alkaline polypeptide fusion protein in preparing targeting tumor cells medicines. In the application, the fusion protein is used as nucleic acid carriers to carry micro-molecules to disturb RNA (such as siRNA) to attack various tumor cells and tissues (such as leukemia stem cell, bladder cancer cell, breast cancer cell and the like) with high expression of FGFR correspondingly; and by inducing the tumor cells to die, restraining the growth and the division of the tumor cells and the like, the growth, the attack and the transference of the tumor cells are restrained at last.

The invention provides an application of miR-99a as an acute myelogenous leukemia stem cell molecular marker and also an application thereof in evaluation of prognosis, disease progression and treatment of the acute myelogenous leukemia. In the application, with flow sorting and real-time fluorescent quantitative PCR technologies as bases and bone marrow miR-99a of leukemia patients as detection objects, through comparison of the expression level between leukemia stem cell and leukemia non-stem cell and the expression level between leukemia stem cell and normal hemopoietic stem cell in the leukemia patients, abnormal high expression of the miR-99a in the leukemia stem cell in relapsed and stubborn patients is found and is related to bad prognosis of the patients, so that the miR-99a, as the marker and molecular target of the leukemia stem cells, is a new molecular marker for prognosis evaluation of the leukemia, and also provides the new molecular target for individual treatment. The application is used for preparing a diagnosis therapy product on the basis of detection on expression of the miR-99a, has important significance and clinical application value for tumor therapy and has wide application prospect.

The invention relates to FGFR3 single-chain antibody-protamine fusion protein and an application thereof. The protein is prepared by the following steps: adding the gene sequence of truncated encoded protamine to the 3' end of a gene for coding the FGFR3 single-chain antibody so as to obtain a fusion gene; cloning the fusion gene to a prokaryotic expression vector and inducing expression in escherichia coli cells; and separating and purifying an inclusion body. The fusion protein can be used as a nucleic acid carrying tool so as to carry small interfering RNA (such as siRNA) to attack various corresponding FGFR3 high-expression tumor cells (such as leukemia stem cell, bladder cancer cell, breast cancer cell and the like); by inducing the apoptosis, growth inhibition, differentiation and the like of tumor cells, finally the effects of inhibiting the growth, invasion and metastasis of tumors can be achieved.

The invention provides methods, uses, kits and compositions comprising a therapeutically effective amount of the microRNA miR-223 for treating myelogenous leukemia in a subject in need of such treatment. The invention further comprises methods encompassing the use of miR-223 for promoting the differentiation of a leukemia stem cell that is resistant to a differentiating agent, and a method of screening for candidate compounds capable of treating a myeloid leukemia by comparison of the therapeutic activity of the candidate compound with the therapeutic activity of miR-233.

In alternative embodiment, provided are methods and compositions for treating, ameliorating or preventing diseases and conditions, such as cancer, including cancers associated with stem cells such as, without limitation, myelodysplastic syndrome (MDS) and a myeloproliferative neoplasm like chronic myeloid leukemia (CML) or acute myeloid leukemia (AML), and ablating or killing cancer stem cells. In alternative embodiment, provided are a new set of biomarkers to detect leukemia stem cell reprogramming and CML progression. In alternative embodiment, provided are therapeutic targets for treating myelodysplastic syndrome (MDS) and chronic myeloid leukemia (CML) by targeting edited let-7 transcripts.

Provided herein are methods for selecting/identifying and/or isolating cancer stem cells from a biological sample or a cell culture sample using a fluorescent glucose analog. Also provided herein are methods for selecting/identifying and/or isolating leukemia stem cells and subpopulations thereof. The present invention is based, in part, on the discovery that cancer stem cells can be selected/identified based upon a lower level of fluorescence of the fluorescent glucose analog compared to non-cancer stem cells and that specific genes are differentially expressed in leukemia stem cells compared to non-leukemia stem cells.

The invention discloses an electrochemical immunosensing method for detecting a leukemia stem cell tumor marker CD123 by a multiple signal amplification technology. The method includes the step of constructing an electrochemical immunosensing method for detecting the leukemia stem cell tumor marker CD123 by utilizing a nanogold material, an aminoterephthalic acid conductive polymer film and an enzyme catalysis multiple signal amplification technology and through detection research on the CD123. Experimental results show that under the optimal experimental condition, a good linear relation is shown between a current signal of the immunosensor and the concentration of CD123 within the concentration range of 0.02-2.5 [mu]g/mL, and the detection limit is as low as 7ng/mL. The established electrochemical immunosensor is stable, reliable, economical and convenient, has the advantages of accuracy, high sensitivity and high specificity, can be well applied to CD123 detection, provides a new detection platform for diagnosis, curative effect judgment and prognosis evaluation of leukemia patients, and has excellent potential clinical application value.

The invention relates to fusion protein of an interleukin-3 derived fragment and a purpose thereof. Particularly, the invention relates to fusion protein containing mutated interleukin-3 derived fragment, which is selected from: (1) IL2mIL3m2SON3, (2) IL2mIL3m3SON3 or (3) IL2mIL3m1SON3, wherein IL2m is an IL2-mutated derived fragment, IL3m2 is an IL3-mutated derived fragment 2, IL3m3 is an IL3-mutated derived fragment 3, and IL3m1 is an IL3-mutated derived fragment 1, and SON3 is a DNA-binding protein SON derivative fragment and is rich in basic amino acids. The invention also related to the purpose of the fusion protein, an encoding nucleotide sequence, a recombinant containing the encoding nucleotide sequence, an engineering cell or engineering bacteria containing the recombinant, a method for production of the fusion protein, a composition of the fusion protein, a compound of the fusion protein, and a purpose of the compound. The invention provides a drug with a fully new mechanism for killing and/or eliminating ordinary leukemia cells and leukemia stem cells.

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.

The invention discloses a preparation method of a racemic beta-aryl-gamma-butyrolactone compound. According to the preparation method, an arylboronic acid compound and gamma, gamma-disubstituted furanone are subjected to an organic catalytic asymmetric Michael addition reaction. According to the efficient preparation method provided by the invention, the gamma-butyrolactone compound reacts with aryl, and the racemic beta-aryl-gamma-butyrolactone compound with a yield as high as 98% is obtained. In addition, an intermediate is provided for preparation of a leukemia stem cell inhibitor with moreeffective activity.

The invention relates to application of miR-31-5p in acute myelogenous leukemia, in particular to application of a product for detecting the miR-31-5p in preparation of a reagent, a chip or a kit for auxiliary diagnosis of subjects suffering from acute myelogenous leukemia (AML) and/or prognosis of the lifetime of the subjects. The invention also relates to an application of the miR-31 initial/precursor miRNA (prime/pre-miR-31) and/or the miR-31 mature miRNA (miR-31-5p) in preparation of a medicine for treating AML (acute myeloid leukemia). The miR-31-5p is introduced into cells through a gene transduction method, so bone marrow AML cells and leukemia stem cells (AML-LSC) can be induced to die, and the cytotoxicity of the chemotherapeutic drug cytarabine is enhanced; by expressing the miR-31-5p, the growth of AML cells and AML-LSC cells can be inhibited, and the life of animals can be prolonged. The disclosure provides a new method for diagnosis and prognosis evaluation of AML, and also provides a gene therapy drug for preparing AML.

The invention relates to a compound and a purpose of the compound for preparing a medicine used for treating a tumor. The above technical scheme can consider that the invention authenticates a micromolecule conditioning agent capable of aiming at JMJD1C, and the JMJD1C micromolecule conditioning agent which takes JDI-10 as a representative can selectively kill leukemia cells and leukemia stem cells but does not affect normal hematopoiesis.