ERBB1/EGFR and JAK3 Tyrosine Kinases as Potential Therapeutic Targets in High-Risk Multiple Myeloma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Data Normalization for Multiple Myeloma (MM) Samples
2.2. Statistical Methods for Differential Gene Expression
2.3. Hierarchical Clustering Analysis
2.4. Overall Survival and Progression-Free Survival Analysis
2.5. Processing of the Multiple Myeloma Research Foundation (MMRF)-CoMMpass RNAseq Dataset
2.6. Overall Survival Analysis and Cox Proportional Hazards Model of the MMRF CoMMpass Study
3. Results
3.1. Amplified Expression of Selective Tyrosine Kinase Genes in Malignant Plasma Cells from MM Patients
3.2. Differentially Amplified Expression of ERBB1/EGFR and JAK3 Genes in Malignant Plasma Cells from High-Risk MM Patients
3.3. Overexpression of EGFR/ERBB1 in MM Cells Is Associated with Augmented Expression of Transcription Factors Binding to Multiple ERBB1 Gene Promoter Sites
3.4. Amplified Expression of ERBB1/EGFR Is Associated with Poor PFS and OS in Newly Diagnosed MM
3.5. Analyses Using the MMRF-CoMMpass RNAseq Dataset for Validation of the Microarray-Based Findings from the HOVON65/GMMG-HD4 Trial Regarding the Prognostic Effect of EGFR/ERBB1 Expression
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Target Kinase | Drug | Brand |
---|---|---|
ABL1, SRC | Bosutinib | Bosulif, SKI-606 |
ABL1, SRC, CKIT | Dasatinib | BMS-354825, Sprycell |
ABL1, SRC | Ponatinib | Iclusig |
EGFR | Gefitinib | ZD1839, Iressa |
EGFR | Dacomitinib | PF-00299804, Visimpro |
EGFR | Erlotinib | OSI-744, Tarceva |
EGFR T790M | Osimertinib | AZD-9292, Tagrisso |
EGFR with exon 20 insertions | Mobocertinib | TAK-788, AP-32788, EXKIVITY |
ErbB1/2/4 | Afatinib | Gilotrif, Tovok |
ErbB1/2/HER2 | Lapatinib | Tykerb |
JAK1 | Upadacitinib | ABT-494, Rinvoq |
JAK1/2 | Baricitinib | Olumiant, LY 3009104 |
JAK1/2/3, Tyk | Ruxolitinib | Jakafi |
JAK2 | Fedratinib | TG101348, Inrebic |
JAK3 | Tofacitinib | Xeljanz |
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Uckun, F.M.; Qazi, S. ERBB1/EGFR and JAK3 Tyrosine Kinases as Potential Therapeutic Targets in High-Risk Multiple Myeloma. Onco 2022, 2, 282-304. https://doi.org/10.3390/onco2040016
Uckun FM, Qazi S. ERBB1/EGFR and JAK3 Tyrosine Kinases as Potential Therapeutic Targets in High-Risk Multiple Myeloma. Onco. 2022; 2(4):282-304. https://doi.org/10.3390/onco2040016
Chicago/Turabian StyleUckun, Fatih M., and Sanjive Qazi. 2022. "ERBB1/EGFR and JAK3 Tyrosine Kinases as Potential Therapeutic Targets in High-Risk Multiple Myeloma" Onco 2, no. 4: 282-304. https://doi.org/10.3390/onco2040016