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AuthorMohamed A., Ismail
AuthorNasrallah, Gheyath K.
AuthorMonne, Maria
AuthorAlSayab, Ali
AuthorYassin, Mohamed A.
AuthorVaradharaj, Govindarajulu
AuthorYounes, Salma
AuthorSorio, Claudio
AuthorCook, Richard
AuthorModjtahedi, Helmout
AuthorAl-Dewik, Nader I.
Available date2022-02-22T10:59:45Z
Publication Date2022-03-01
Publication NameGene
Identifierhttp://dx.doi.org/10.1016/j.gene.2021.146101
CitationIsmail, M. A., Nasrallah, G. K., Monne, M., AlSayab, A., Yassin, M. A., Varadharaj, G., Younes, S., Sorio, C., Cook, R., Modjtahedi, H., & Al-Dewik, N. I. (2022). Description of PTPRG genetic variants identified in a cohort of Chronic Myeloid Leukemia patients and their ability to influence response to Tyrosine kinase Inhibitors. Gene, 813, 146101. https://doi.org/10.1016/j.gene.2021.146101
ISSN03781119
URIhttps://www.sciencedirect.com/science/article/pii/S037811192100696X
URIhttp://hdl.handle.net/10576/27395
AbstractTyrosine kinase inhibitors (TKIs) have remarkably transformed Ph+ chronic myeloid leukemia (CML) management; however, TKI resistance remains a major clinical challenge. Mutations in BCR-ABL1 are well studied but fail to explain 20–40% of resistant cases, suggesting the activation of alternative, BCR-ABL1-independent pathways. Protein Tyrosine Phosphatase Receptor Gamma (PTPRG), a tumor suppressor, was found to be well expressed in CML patients responsive to TKIs and remained at low level in resistant patients. In this study, we aimed to identify genetic variants in PTPRG that could potentially modulate TKIs response in CML patients. DNA was extracted from peripheral blood samples collected from two CML cohorts (Qatar and Italy) and targeted exome sequencing was performed. Among 31 CML patients, six were TKI-responders and 25 were TKI-non-responsive. Sequencing identified ten variants, seven were annotated and three were novel SNPs (c.1602_1603insC, c.85+14412delC, and c.2289-129delA). Among them, five variants were identified in 15 resistant cases. Of these, one novel exon variant (c.1602_1603insC), c.841-29C>T (rs199917960) and c.1378-224A>G (rs2063204) were found to be significantly different between the resistant cases compared to responders. Our findings suggest that PTPRG variants may act as an indirect resistance mechanism of BCR-ABL1 to affect TKI treatment.
SponsorThis work was supported by the National Priorities Research Program (NPRP) grant number 4-157-3–052.
Languageen
PublisherElsevier
SubjectChronic Myeloid Leukemia
Protein Tyrosine Phosphatase Receptor Type G
BCR-ABL1
Single Nucleotide Polymorphisms
Tyrosine Kinase Inhibitors
Therapeutic Modalities
TitleDescription of PTPRG genetic variants identified in a cohort of Chronic Myeloid Leukemia patients and their ability to influence response to Tyrosine kinase Inhibitors
TypeArticle
Volume Number813
Open Access user License http://creativecommons.org/licenses/by/4.0/
dc.accessType Open Access


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