NPM Mutants as Molecular Markers for AML Diagnosis

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Solution Overview

Problem

Current diagnostic and therapeutic approaches for acute myeloid leukemia (AML) with normal karyotype lack specific molecular markers, making it difficult to accurately diagnose, monitor minimal residual disease, and develop targeted therapies.

Innovation Solution

Identification of new mutants of the nucleophosmin protein (NPM) and their corresponding gene sequences, which are specifically associated with normal karyotype AML, serving as markers for diagnosis, prognosis, and therapy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional diagnostic approaches are used for AML with normal karyotype, then general leukemia diagnosis can be achieved, but specific molecular markers for accurate diagnosis and monitoring are lacking

Engineering Contradiction:

Improvediagnostic accuracyVSAvoidlack of specific molecular markers

Core Design Contradiction:

Measurement precisionVSLoss of information

Solution Approach 1:

The patent introduces NPM mutants as intermediary molecular markers that bridge the gap between conventional diagnostic methods and the need for specific detection in normal karyotype AML. These mutants serve as detectable intermediaries that provide the missing molecular specificity without requiring chromosomal abnormalities.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention detects specific parameter changes in the NPM protein (mutations in exon 12 leading to cytoplasmic localization) that are characteristic of normal karyotype AML. By focusing on these specific molecular parameters rather than general morphological features, the patent achieves higher diagnostic precision.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If chemotherapy is used to treat AML, then leukaemic cells can be destroyed, but monitoring minimal residual disease becomes difficult without specific markers

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidminimal residual disease detection

Core Design Contradiction:

ReliabilityVSDifficulty of detecting and measuring

Solution Approach 1:

The patent replaces morphological assessment methods with molecular detection methods for monitoring treatment response. Instead of relying on visual examination of blood smears or bone marrow aspirates, the invention uses molecular techniques to detect NPM mutant transcripts, providing objective and sensitive measurement of minimal residual disease.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Adaptability or versatility

If targeted therapy is developed based on genetic lesions, then treatment specificity can be improved, but this requires identification of specific molecular targets which are currently unavailable in normal karyotype AML

Engineering Contradiction:

Improvetherapy targeting capabilityVSAvoidabsence of molecular targets

Core Design Contradiction:

Adaptability or versatilityVSLoss of information

Solution Approach 1:

The patent extracts and isolates the NPM mutant as a specific therapeutic target from the complex background of normal karyotype AML. By focusing on this specific molecular abnormality, the invention creates a basis for targeted therapy development, separating the detectable molecular feature from the overall disease presentation.

Inventive Principle:

Principle #2Taking out (Extraction)

Data Source

PatentUS20250154599A1Nucleophosmin protein (NPM) mutants, corresponding gene sequences and uses thereof

Publication Date: 2025.05.15 FALINI BRUNANGELO

AI summary

The invention relates to new nucleophosmin protein (NPM) mutants, corresponding gene sequences and relative uses thereof for diagnosis, monitoring of minimal residual disease, prognostic evaluation and therapy of acute myeloid leukaemia (AML).