Disease Information

General Information of the Disease (ID: DIS00552)

• Name: Mature B-cell neoplasms
• ICD: ICD-11: 2A8Z

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Inotuzumab ozogamicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Serine-protein kinase ATM (ATM) [1]

• Resistant Disease: Mature B-cell neoplasms [.]
• Resistant Drug: Inotuzumab ozogamicin
• Molecule Alteration: Missense mutation; Methylation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: pre-InO and/or post-InO tumor cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: GeneSeq assay; Mutation assay
• Mechanism Description: Multiple mechanisms drive CD22 antigen escape, including epitope loss (protein truncation and destabilization) and epitope alteration.Hypermutation caused by error-prone DNA damage repair may serve as a driver of CD22 mutation and escape.

Key Molecule: Cyclin-dependent kinase inhibitor 2A (CDKN2A) [1]

• Resistant Disease: Mature B-cell neoplasms [.]
• Resistant Drug: Inotuzumab ozogamicin
• Molecule Alteration: Missense mutation; Activation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: pre-InO and/or post-InO tumor cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: GeneSeq assay; Mutation assay
• Mechanism Description: Multiple mechanisms drive CD22 antigen escape, including epitope loss (protein truncation and destabilization) and epitope alteration.Hypermutation caused by error-prone DNA damage repair may serve as a driver of CD22 mutation and escape.

Key Molecule: B-cell receptor CD22 (CD22) [1]

• Resistant Disease: Mature B-cell neoplasms [.]
• Resistant Drug: Inotuzumab ozogamicin
• Molecule Alteration: Missense mutation; Amplification
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: pre-InO and/or post-InO tumor cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: GeneSeq assay; Mutation assay
• Mechanism Description: Multiple mechanisms drive CD22 antigen escape, including epitope loss (protein truncation and destabilization) and epitope alteration.Hypermutation caused by error-prone DNA damage repair may serve as a driver of CD22 mutation and escape.

Key Molecule: Tumor protein p53 (TP53) [1]

• Resistant Disease: Mature B-cell neoplasms [.]
• Resistant Drug: Inotuzumab ozogamicin
• Molecule Alteration: Missense mutation; Methylation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: pre-InO and/or post-InO tumor cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: GeneSeq assay; Mutation assay
• Mechanism Description: Multiple mechanisms drive CD22 antigen escape, including epitope loss (protein truncation and destabilization) and epitope alteration.Hypermutation caused by error-prone DNA damage repair may serve as a driver of CD22 mutation and escape.

Key Molecule: Histone-lysine N-methyltransferase 2D (KMT2D) [1]

• Resistant Disease: Mature B-cell neoplasms [.]
• Resistant Drug: Inotuzumab ozogamicin
• Molecule Alteration: Missense mutation; Loss
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: pre-InO and/or post-InO tumor cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: GeneSeq assay; Mutation assay
• Mechanism Description: Multiple mechanisms drive CD22 antigen escape, including epitope loss (protein truncation and destabilization) and epitope alteration.Hypermutation caused by error-prone DNA damage repair may serve as a driver of CD22 mutation and escape.

Key Molecule: DNA nucleotidylexotransferase (DNTT) [1]

• Resistant Disease: Mature B-cell neoplasms [.]
• Resistant Drug: Inotuzumab ozogamicin
• Molecule Alteration: Missense mutation; p.R183W
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: pre-InO and/or post-InO tumor cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: GeneSeq assay; Mutation assay
• Mechanism Description: Multiple mechanisms drive CD22 antigen escape, including epitope loss (protein truncation and destabilization) and epitope alteration.Hypermutation caused by error-prone DNA damage repair may serve as a driver of CD22 mutation and escape.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Multidrug resistance-associated protein 1 (MRP1) [1]

• Sensitive Disease: Mature B-cell neoplasms [.]
• Sensitive Drug: Inotuzumab ozogamicin
• Molecule Alteration: Function; C2617T/A; A2063G
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: pre-InO and/or post-InO tumor cells; N.A.; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: GeneSeq assay; Mutation assay
• Mechanism Description: Multiple mechanisms drive CD22 antigen escape, including epitope loss (protein truncation and destabilization) and epitope alteration.Hypermutation caused by error-prone DNA damage repair may serve as a driver of CD22 mutation and escape.

References

• Ref 1: Genomic determinants of response and resistance to inotuzumab ozogamicin in B-cell ALL. Blood. 2024 Jul 4;144(1):61-73.