Composite profiles of cell antigens and target signal transduction proteins for analysis and clinical management of hematologic cancers

A target protein and protein technology, which is applied in the field of complex distribution of cell antigens and target signal transduction proteins for blood cancer analysis and clinical treatment, can solve the problems of not getting better results, not receiving treatment, and not being able to prolong survival

Inactive Publication Date: 2009-03-18
BECKMAN COULTER INC +4
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These treatments can take a severe physical and emotional toll on patients without the necessary improvement; in some cases, B-CLL patients even die from the harshness of these treatments rather than from B-CLL. Impact of CLL
Patients in the early stage of B-CLL, because of their better physiological status, can receive aggressive or experimental treatment, as long as the status remains stable, they usually do not receive treatment, for two reasons: first, currently available treatments do not prolong survival; second, it does not yet provide a reliable indication of whether early-stage patients will get better or worse

Method used

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  • Composite profiles of cell antigens and target signal transduction proteins for analysis and clinical management of hematologic cancers
  • Composite profiles of cell antigens and target signal transduction proteins for analysis and clinical management of hematologic cancers
  • Composite profiles of cell antigens and target signal transduction proteins for analysis and clinical management of hematologic cancers

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0085] Prepare samples for building composite distributions

[0086] This example shows the sample preparation procedure used to establish a composite profile for an individual suspected of having B-cell chronic lymphocytic leukemia (B-CLL).

[0087] In summary, 10 μl of reagent mixed with cell surface markers CD5-FITC, +CD3-ECD, +CD56-PC5, +CD19-PC7 was added to vials and 100 μl of whole blood was added. Incubate at room temperature for 20 min, add 64 μl of fixative solution (10% formaldehyde) and incubate at room temperature for 10 min. Next, 1 mL of lysis / permeabilization reagent (0.1% Triton X-100) was added, incubated at room temperature for 30 min, and then centrifuged. Wash the cells twice with buffer (PBS containing 2% BSA), resuspend with 10 μl anti-ZAP-70-PE and 90 μl buffer, incubate at room temperature for 30 min, then wash once with buffer, wash with 0.1% polysaccharide Resuspend in formaldehyde buffer. Samples were then analyzed by flow cytometry. figure 1 ...

Embodiment 2

[0089] Analysis of samples used to create composite distributions

[0090] This example shows the analysis of samples by flow cytometry to create a composite profile.

[0091] As shown in Figure 2, the ZAP-70 gating / analysis algorithm was used to build the composite distribution as follows: the first gate of normal whole blood samples was used to identify lymphocytes (blue plus green) by light scattering, as shown in the upper left histogram Show. If desired, CD45 side scatter (linear scale) can be used to gate CD45-bright lymphocytes in peripheral blood for CD4 enumeration, while CD45 side scatter (log scale) can be used to identify bone marrow mesoderm group for phenotyping. In Figure 2, a histogram of CD19 versus CD5 identifies normal B cells (purple, upper left quadrant), normal T cells (blue, lower right quadrant), and "pre" B cells in normal peripheral blood (CD19+5+, upper right quadrant). B-CLL neoplastic transformed cells also fell into the upper right quadrant,...

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Abstract

The present invention provides methods for establishing a composite marker profile for a sample derived from an individual suspected having a neoplastic condition. A composite marker profile of the invention allows for identification of prognostically and therapeutically relevant subgroups of neoplastic conditions and prediction of the clinical course of an individual. The methods of the invention provide tools useful in choosing a therapy for an individual afflicted with a neoplastic condition, including methods for assigning a risk group, methods of predicting an increased risk of relapse, methods of predicting an increased risk of developing secondary complications, methods of choosing a therapy for an individual, methods of determining the efficacy of a therapy in an individual, and methods of determining the prognosis for an individual. In particular, the method of the present invention discloses a method for establishing a composite marker profile that can serve as a prognostic indicator to predict whether the course of a neoplastic condition in a individual will be aggressive or indolent, thereby aiding the clinician in managing the patient and evaluating the modality of treatment to be used. In particular embodiments disclosed herein, the methods of the invention are directed to establishing a composite marker profile for a leukemia selected from the group consisting of Chronic Lymphocytic Leukemia (CLL), Acute Myelogenous Leukemia (AML), Chronic Myelogenous Leukemia (CML), and Acute Lymphocytic Leukemia (ALL).

Description

Background technique [0001] Leukemia is a malignant cancer of the bone marrow and blood. Leukemia is characterized by an overgrowth of abnormal white blood cells that fill the bone marrow and / or peripheral blood. This results in reduced growth and weakened function of normal blood cells. Chronic lymphocytic leukemia (CLL) is one of four major types of leukemia that afflict humans, the others being acute myeloid leukemia (AML), chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). [0002] Leukemic patients undergo a diverse clinical course. Treatment of leukemia is complex and depends on the type of leukemia. Substantial clinical variability in remission was found in leukemia patients, even among those who received a single course of treatment. Some patients can survive for a long time without definitive treatment, while others die quickly after aggressive treatment. Those who are resistant to treatment survive only short periods of time, regardless o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/53G01N33/574C12N5/07C12N5/0781C12N5/09
CPCG01N33/5052G01N33/57426G01N2800/52
Inventor 查尔斯·古尔斯比文森特·T·尚奇戴维·赫德利詹姆斯·雅克伯格斯坦利·沙克尼
Owner BECKMAN COULTER INC
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