Flow Cytometry MRD Detection Panel for ALL
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Solution Overview
Problem
Current methods for detecting minimal residual disease in acute lymphoblastic leukemia (ALL) are limited by the need for specialized expertise and instrumentation, and their applicability is restricted due to the requirement for specific molecular targets, which are not present in all patients, making it difficult to extend the benefit of minimal residual disease monitoring to all patients.
Innovation Solution
The use of a panel of probes specifically binding to markers such as CD19, CD10, CD34, CD45, and additional markers like CD38, CD24, CD44, CD58, CD73, CD15, CD200, CD123, CD86, CD72, CD13, CD33, CD79b, HSPB1, BCL2, CD164, CD304, CD97, CD102, or CD300a to detect minimal residual disease through flow cytometry, allowing for the identification of leukemic cells even in low concentrations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If PCR amplification of antigen-receptor genes is used for MRD detection, then detection sensitivity is improved, but device complexity and requirement for specialized expertise increase
Solution Approach 1:
The patent replaces complex molecular biology techniques (PCR amplification) with flow cytometry-based immunophenotypic analysis. This substitution maintains high detection sensitivity while reducing the need for specialized instrumentation and expertise, as flow cytometry is more widely available in clinical laboratories.
Solution Approach 2:
The patent employs commercially available fluorescently labeled antibodies and standardized flow cytometry protocols instead of requiring expensive, specialized molecular biology equipment. This approach reduces the barrier to entry and enables broader application in routine clinical settings.
2Loss of information
If PCR amplification of fusion transcripts is used for MRD detection, then molecular information is obtained, but applicability is restricted to patients with specific molecular targets
Solution Approach 1:
The patent establishes a universal approach using flow cytometry to detect immunophenotypic markers that are present across all B-cell precursor ALL patients, regardless of their specific molecular genetics. This multi-functional method can identify leukemic cells in patients with any molecular subtype, making it universally applicable while still providing valuable molecular information through marker expression patterns.
Solution Approach 2:
The patent shifts the detection parameter from molecular genetics (PCR amplification of fusion transcripts) to immunophenotypic parameters (flow cytometric detection of surface markers). This parameter change enables detection across all patient types without being limited by the presence or absence of specific fusion genes or molecular targets.
3Adaptability or versatility
If standard flow cytometry is used for MRD detection, then wider applicability is achieved, but detection sensitivity is limited
Solution Approach 1:
The patent segments the detection approach into multiple components: using multiple fluorescently labeled antibodies against specific immunophenotypic markers, implementing compensatory fluorescence controls, and applying sophisticated data analysis algorithms. This segmentation enables standard flow cytometry instruments to achieve enhanced detection sensitivity while maintaining broad applicability.
Solution Approach 2:
The patent optimizes detection sensitivity by changing the immunophenotypic parameters being measured, selecting markers with optimal expression characteristics in ALL cells versus normal cells. This parameter optimization allows standard flow cytometry to detect minimal residual disease with high sensitivity across all patient populations.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach enhances the sensitivity of minimal residual disease detection, enabling the identification of one leukemic cell in 100,000 normal bone marrow cells, thereby improving the monitoring of ALL and extending its applicability to all patients, regardless of the presence of specific molecular targets.
Implementation Method 1
contacting a specimen from a patient with a plurality of probes, wherein each of said probes specifically binds to a distinct marker
Implementation Method 2
The complex formed between each of the probes and their marker is detected and a value is generated corresponding to an expression level of each of said marker
Data Source
AI summary
This invention provides methods and kits for diagnosing, ascertaining the clinical course of minimal residual disease associated with acute lymphoblastic leukemia (ALL). Specifically the invention provides methods and kits useful in the diagnosis and determination of clinical parameters associated with diseases associated with ALL based on patterns of surface marker expression unique to ALL.