53 results about "Leukemia Stem Cell" patented technology

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.

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 relates to compounds and methods which are useful in molecular investigations of target genes, as well as their encoded RNAs and protein, belonging to signature self renewal programs in leukemia and / or cancer stem cells. Data herein shows that leukemia stem cells can be generated from committed progenitors without widespread reprogramming of gene expression, and wherein a leukemia self-renewal associated signature is activated in the process.

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.

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.

Compositions and methods are provided for eliciting antigen-specific T-cell responses against human cyclin A1 (CCNA1), which is herein identified as a leukemia-associated antigen based on its overexpression in acute myeloid leukemia (AML) including leukemia stem cells (LSC) and in immunologically privileged testis cells, but not in other normal cell types. CCNA1-derived peptide epitopes that are immunogenic for T-cells including CTL are disclosed, as are immunotherapeutic approaches using such peptides for vaccines and generation of adoptive transfer therapeutic cells.

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 method for separating leukemia stem cells from a leukemia cell strain, which comprises the following steps: firstly, subculturing human acute myelogenous leukemia cell strain KD1a cells; and secondly, separating CD34+CD38-cells by an immunomagnetic bead separation method to obtain the leukemia stem cells, wherein the leukemia stem cells can resist conventional chemotherapy and NK immunization therapy. The separation method disclosed by the invention is simple to operate, can separate a large quantity of high-purity leukemia stem cells from KG1a cells, and has an important significance for the research of the leukemia stem cells.

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 an anti-human CD45RA rat immune globulin variable region gene, which comprises nucleotide sequences of SEQIDNO.1 and SEQIDNO.2 and encoded nucleotide sequences of SEQIDNO.3 and SEQIDNO.4. Research proves that anti-human CD45RA rat immune globulin variable region gene can effectively distinguish leukemia patients, leukemia cell strain CD34+CD38-CD123+leukemia stem cells and CD34+CD38+CD123+ offspring leukemia cells, has the application prospects of leukemia targeted therapy, and can be used in preparing targeted therapy blood system malignant tumor medicines.

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 invention discloses a mouse model for resisting to MLL leukemia by changing an epigenetic modification level as well as a establishing method and application of the mouse model. A Histone lysine methyltransferase Suv39h1 gene for increasing an H3k9me3 level is introduced to an MLL leukemia cell by utilizing a lentiirus-mediated gene introduction technology, and then, the gene-introduced MLL leukemia cell is transferred to a receptor mouse subjected to half lethal dose irradiation, and thus, the mouse model for resisting to MLL leukemia. The mouse is embodied in significant prolonging of lifetime as well as number reduction and function lowering of leukemia stem cells. The mouse model can be used for simply, rapidly and efficiently realizing qualitative and / or quantitative evaluation ofpotential drugs for treating MLL leukemia.

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.

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 relates to an application of an anti-PTN antibody to inhibition of leukemia stem cells and treatment of chronic granulocytic leukemia, and the anti-PTN antibody can be combined with PAI-1 protein with high affinity, inhibit implantation of CML stem cells, and inhibit growth of CML stem cells. The antibody can be used for preventing or treating chronic granulocytic leukemia, and has awide application prospect.

Described herein are methods for treating or preventing leukemias with NK-92 cells. In particular, provided are methods of treating or preventing leukemias by administering to a patient one or more doses of NK-92 cells for killing remnant (also referred to as residual) leukemia cells and / or leukemia stem cells. In various embodiments, NK-92 cells are administered to a patient to treat and / or prevent leukemia that is refractory or resistant, or has relapsed in a patient who is recovering from treatment for leukemia under conventional therapies.

Using the methods of the present invention, intermediate (int) levels of aldehyde dehydrogenase (ALDH) activity reliably distinguished leukemic CD34+CD38− cells capable of engrafting immunodeficient mice, from residual normal hematopoietic stem cells that exhibited relatively higher ALDH activity. Minimal residual disease (MRD) detected during complete remission was enriched for the CD34+CD38−ALDHint leukemic cells, and the presence of these cells after therapy highly correlated with subsequent clinical relapse. The methods of the present invention can distinguish normal from leukemic CD34+CD38− cells, and identifies those AML cells associated with relapse. Methods of prediction of relapse of AML patients and methods of treatment are also provided.

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 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.

Compositions and methods are provided for eliciting antigen-specific T-cell responses against human cyclin A1 (CCNA1), which is herein identified as a leukemia-associated antigen based on its overexpression in acute myeloid leukemia (AML) including leukemia stem cells (LSC) and in immunologically privileged testis cells, but not in other normal cell types. CCNA1-derived peptide epitopes that are immunogenic for T-cells including CTL are disclosed, as are immunotherapeutic approaches using such peptides for vaccines and generation of adoptive transfer therapeutic cells.

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 present invention provides an invasive cancer stem cell (iCSC) or a substantively homogeneous cell population including said iCSC based on a cell-surface biomarker specifically localizing to the invadopodia of said iCSC. The present invention further provides an invasive leukemia stem cell (iLSC) or a substantively homogeneous cell population including said iLSC based on a cell-surface biomarker specifically localizing to the invadopodia of said iLSC. The present invention also provides a method or a kit of determining a diagnosis of aggressive solid tumor or hematopoietic cancer.