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Adult T-cell leukemia / lymphoma (ATLL) is an aggressive T-cell malignancy that often has a poor prognosis with current therapies
Adult T-cell leukemia / lymphoma (ATLL) is an aggressive T-cell malignancy that often has a poor prognosis with current therapies
Scientists identify novel genetic target for treating adult blood cancer
Scientists identify novel genetic target for treating adult blood cancer
Image credit: Takashi Ishio, et al.
ATLL is a malignant blood cancer related to viral infection .
In this study, researcher Masao Nakagawa and colleagues used CRISPR-Cas9 gene editing technology to manipulate the expression of thousands of genes in various ATLL cell lines, aiming to elucidate the effect of drugs that kill ATLL cells.
One of these genes proved to be a promising drug target, the CDK6 gene, which encodes a specific enzyme that activates cell proliferation .
Importantly, the researchers also found that combining the drug palbociclib with everolimus (used to treat kidney and breast cancer) may kill ATLL cells including TP53 mutations; When tested in mice with ATLL tumors, the drug combination may significantly reduce tumor growth with fewer side effects; everolimus inhibits the function of the protein complex mTORC1, which is mainly involved in maintaining cell growth.
Image credit: https://ashpublications.
Image credit: https://ashpublications.
"Our findings suggest that CDK6 may be a very attractive target for the treatment of ATLL, and that in some ATLL cell lines, loss of TP53 function may render cells resistant to the CDK6 inhibitor Palbociclib," said researcher Nakagawa.
Taken together, the results of this study define CDK6 as a possible novel therapeutic target for ATLL, and support further evaluation of the therapeutic effect of palbociclib combined with mTORC1 inhibitors in the treatment of refractory tumors
Original source:
Takashi Ishio, Sarvesh Kumar, Joji Shimono, et al.
Takashi Ishio, Sarvesh Kumar, Joji Shimono, et al.
Genome-wide CRISPR screen identifies CDK6 as a therapeutic target in adult T-cell leukemia/lymphoma , Blood (2021).
DOI: 10.
1182/blood.
2021012734 Genome-wide CRISPR screen identifies CDK6 as a therapeutic target in adult T-cell leukemia/lymphoma Blood
