Cobll1 Biomarker for CML Blast Crisis Prediction

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Solution Overview

Problem

Current methods for diagnosing chronic myeloid leukemia (CML) rely heavily on detecting the BCR-ABL1 mutation, but fail to effectively predict transformation to acute phases, resistance to tyrosine kinase inhibitors, and prognosis, especially in cases without BCR-ABL1 mutations.

Innovation Solution

Measuring the expression level of Cordon-bleu protein-like 1 (Cobll1) in biological samples using various analysis methods and kits, which includes the use of specific probes, primers, antibodies, and oligonucleotides to diagnose CML progression, predict prognosis, and assess resistance to tyrosine kinase inhibitors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If BCR-ABL1 mutation detection is used for diagnosing chronic myeloid leukemia, then diagnostic accuracy for typical CML cases is improved, but the ability to predict transformation to acute phases and drug resistance is insufficient

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidprognostic information
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The patent applies multi-functionality by using the Cobll1 marker to perform multiple diagnostic and prognostic functions simultaneously. Instead of relying solely on BCR-ABL1 for diagnosis, the Cobll1 marker serves universal purposes including diagnosing CML, predicting transformation to acute phases, assessing drug resistance, and evaluating prognosis, thereby eliminating the need for multiple separate tests and comprehensively addressing both diagnostic accuracy and prognostic information needs

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Productivity

If BCR-ABL1-based diagnostic methods are used, then typical CML cases can be identified, but cases without BCR-ABL1 mutations or with alternative resistance mechanisms are missed

Engineering Contradiction:
Improvediagnosis efficiencyVSAvoiddiagnostic coverage
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent applies parameter changes by shifting the diagnostic parameter from BCR-ABL1 mutation status to Cobll1 expression levels. This parameter change enables the detection of CML cases that lack BCR-ABL1 mutations and identifies patients with alternative resistance mechanisms, thereby expanding diagnostic coverage while maintaining diagnostic efficiency through a standardized measurement approach

Inventive Principle:
Principle #35Parameter changes

3Reliability

If tyrosine kinase inhibitors are used to treat chronic myeloid leukemia, then disease control is improved, but resistance develops in some patients

Engineering Contradiction:
Improvetreatment efficacyVSAvoidtreatment duration
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent applies preliminary action by measuring Cobll1 expression levels before initiating tyrosine kinase inhibitor treatment and at various intervals during treatment. This preliminary and ongoing assessment allows for early identification of patients who are likely to develop resistance, enabling clinicians to adjust treatment strategies proactively before complete treatment failure occurs, thereby extending effective treatment duration

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentEP3336548B1Method for providing information on chronic myeloid leukemia
Publication Date: 2021.04.14 RES & BUSINESS FOUND SUNGKYUNKWAN UNIV
  • EP3336548B1 patent drawingFigure 1A
  • EP3336548B1 patent drawingFigure 1B
  • EP3336548B1 patent drawingFigure 1C

AI summary

The present invention relates to a method of providing information on chronic myeloid leukemia by use of Cordon-bleu protein-like 1 (Cobll1). More specifically, the method of the present invention can simultaneously provide various information such as diagnosis of the transformation of chronic myeloid leukemia to an acute phase (progression to blast crisis, BC), prediction of prognosis after the transformation of chronic myeloid leukemia to an acute phase (progression to blast crisis, BC), the resistance of chronic myeloid leukemia to various therapeutic drugs, including tyrosine kinase inhibitors, and may also be used to diagnose patients who could not be predicted and diagnosed by measurement of the expression level of the BCR-ABL1 gene according to the prior art. Thus, it is expected that the method of the present invention can be used to predict and diagnose various prognoses, including the progression, recurrence and drug resistance of chronic myeloid leukemia. Furthermore, it is expected that the use of the oligonucleotide of the present invention, which binds specifically to Cobll1 mRNA, can effectively inhibit expression of the Cobll1 protein so as to effectively inhibit cell proliferation and drug resistance, thereby treating chronic myeloid leukemia and effectively inhibiting the transformation of chronic myeloid leukemia to an acute phase (progression to blast crisis, BC).