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A germline point mutation in the MYC-FBW7 phosphodegron initiates hematopoietic malignancies.
Genes Dev
April 2024
Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington 98109, USA;
Oncogenic activation of MYC in cancers predominantly involves increased transcription rather than coding region mutations. However, MYC-dependent lymphomas frequently acquire point mutations in the MYC phosphodegron, including at threonine 58 (T58), where phosphorylation permits binding via the FBW7 ubiquitin ligase triggering MYC degradation. To understand how T58 phosphorylation functions in normal cell physiology, we introduced an alanine mutation at T58 (T58A) into the endogenous locus in the mouse germline.
View Article and Find Full Text PDFA Germline Point Mutation in the MYC-FBW7 Phosphodegron Initiates Hematopoietic Malignancies.
bioRxiv
October 2023
Basic Sciences Division, Fred Hutchinson Cancer Center, Seattle WA, USA.
Oncogenic activation of MYC in cancers predominantly involves increased transcription rather than coding region mutations. However, MYC-dependent lymphomas frequently contain point mutations in the MYC phospho-degron, including at threonine-58 (T58), where phosphorylation permits binding by the FBW7 ubiquitin ligase triggering MYC degradation. To understand how T58 phosphorylation functions in normal cell physiology, we introduced an alanine mutation at T58 (T58A) into the endogenous locus in the mouse germline.
View Article and Find Full Text PDFIdentification of Cell Type-Specific Effects of Mutations on Relapse in Acute Myeloid Leukemia.
Mol Cells
October 2023
School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea.
Article Synopsis
- Acute myeloid leukemia (AML) is a complex disease with unique genetic mutations in each patient, leading to varied cell compositions and a high risk of relapse even after achieving complete remission through chemotherapy.
- Researchers used single-cell RNA sequencing on bone marrow cells from patients at different AML stages to identify abnormalities in hematopoietic stem cells (HSCs) and track the presence of specific mutations over time.
- The study revealed that certain progenitor cells (GMPs and LMPPs) persist through treatment and are linked to relapse, highlighting the importance of understanding these cell types for better predicting outcomes in AML.
Therapeutic potentials of melatonin in the treatment of lymphoma: A review of current evidence.
Fundam Clin Pharmacol
October 2022
Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.
Hematological malignancies including leukemia, multiple myeloma, and lymphoma are known as leading causes of death around the world. Despite all developments in cancer management, current therapeutic methods are still relatively inefficient, leading to the heavy financial burdens for public health systems. Strategic attempts in clinical practice must be based on three serious goals including (1) increasing the efficacy of treatments and decreasing their side-effects; (2) decreasing financial price of treatments and related morbidity and mortality rates; and (3) improving life quality and survival of affected patients.
View Article and Find Full Text PDFCombination of Estradiol with Leukemia Inhibitory Factor Stimulates Granulosa Cells Differentiation into Oocyte-Like Cells.
Adv Pharm Bull
September 2021
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Article Synopsis
- Recent research indicates that cumulus granulosa cells (GCs) can transform into various non-ovarian cells and this study aims to evaluate their potential to differentiate into oocyte-like cells.
- The experiment involved isolating GCs from healthy women and testing different media with factors like leukemia inhibitory factors (LIFs) and estradiol to observe changes in specific gene expressions and cell morphology.
- Results showed that LIFs promote the expression of the stemness factor Oct3/4, while estradiol enhances genes associated with oocyte development, suggesting a combination of these factors may offer therapeutic options for gynecological issues.*
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