Beyond KIT in CBF-AML: chromatin and cohesin

Rau, Rachel E.

doi:10.1182/blood-2016-03-707083

Cited by 7 publications

(10 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is increasing evidence of genetic heterogeneity of CBF AML, which may be mainly driven by synergistic genetic or epigenetic events, these events are certainly present because the CBF AML fusion gene is necessary, but not sufficient, for leukogenesis (30). In addition to the known secondary chromosomal aberrations, RAS-KIT and FLT3 gene mutations have been found to be the most common molecular alteration in CBF AML (16,59).…”

Section: Discussionmentioning

confidence: 99%

“…For example, ASXL2, ZBTB7A and cohesin mutations were found exclusively in t(8;21) AML, although none had an impact on overall or event-free survival (20,21,28,29). In addition, although both types share tyrosine kinase (TK) mutations, there are significant differences in the incidence and prognosis of mutations in patients with both subtypes (30). Recently, data on CBF AML in Asian countries have been reported.…”

Section: Heterogeneity Of Common Mutant Genes Between Two Subtypes Of Cbf Amlmentioning

confidence: 99%

“…Regarding the FLT3 mutation in patients with CBF AML, studies have suggested that FLT3 mutation may play an important role in the leukogenesis in CBF AML, because FLT3 and t(8;21) AML fusion gene (CBFB-MYH11) interaction can induce mouse leukemia phenotype (53,54). It has been found that FLT3-TKD in CBF AML may make the cells resistant to chemotherapy, and even if the low-frequency clone after treatment is retained, it will appear as the main clone in subsequent recurrence (30). There have been a number of retrospective studies reporting that FLT3 mutation in patients with inv ( 16) is more common than that in patients with t(8;21) (46,55).…”

Section: Cbf Aml and Kit Mutationsmentioning

confidence: 99%

See 2 more Smart Citations

Core binding factor acute myeloid leukemia: Advances in the heterogeneity of KIT, FLT3, and RAS mutations (Review)

Quan

Deng

2020

Mol Clin Oncol

View full text Add to dashboard Cite

Core binding factor (CBF) is a heterodimer protein complex involved in the transcriptional regulation of normal hematopoietic process. In addition, CBF molecular aberrations represent approximately 20% of all adult Acute Myeloid Leukemia (AML) patients. Treated with standard therapy, adult CBF AML has higher complete remission (CR) rate, longer CR duration, and better prognosis than that of AML patients with normal karyotype or other chromosomal aberrations. Although the prognosis of CBF AML is better than other subtypes of adult AML, it is still a group of heterogeneous diseases, and the prognosis is often different. Recurrence and relapse-related death are the main challenges to be faced following treatment. Mounting research shows the gene heterogeneity of CBF AML. Therefore, to achieve an improved clinical outcome, the differences in clinical and genotypic characteristics should be taken into account in the evaluation and management of such patients, so as to further improve the risk stratification of prognosis and develop targeted therapy. The present article is a comprehensive review of the differences in some common mutant genes between two subtypes of CBF AML.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Heterogeneity Of Common Mutant Genes Between Two Subtypes Of Cbf Amlmentioning

confidence: 99%

Section: Cbf Aml and Kit Mutationsmentioning

confidence: 99%

See 1 more Smart Citation

Core binding factor acute myeloid leukemia: Advances in the heterogeneity of KIT, FLT3, and RAS mutations (Review)

Quan

Deng

2020

Mol Clin Oncol

View full text Add to dashboard Cite

show abstract

“…4 CBF-AML encodes two recurrent cytogenetic abnormalities referred to as t(8; 21)q (22;22) and inv (16). 5 The t(8; 21)q(22;22) is a common translocation identified in 40-50% of FAB-M2b subtype, and rare cases of M0, M1, and M4 subtypes. 6 Meanwhile, the inv (16) occurs in 5% of AML cases.…”

Section: Introductionmentioning

confidence: 99%

Natural HDAC‐1/8 inhibitor baicalein exerts therapeutic effect in CBF‐AML

et al. 2020

Clinical & Translational Med

View full text Add to dashboard Cite

Background Although targeting histone deacetylases (HDACs) may be an effective strategy for core binding factor‐acute myeloid leukemia (CBF‐AML) harboring t(8;21) or inv(16), HDAC inhibitors are reported to be limited by drug‐resistant characteristic. Our purpose is to evaluate the anti‐leukemia effects of Baicalein on CBF‐AML and clarify its underlying mechanism. Methods Enzyme activity assay was used to measure the activity inhibition of HDACs. Rhodamine123 and RT‐qPCR were employed to evaluate the distribution of drugs and the change of ATP‐binding cassette (ABC) transporter genes. CCK8, Annexin V/PI, and FACS staining certified the effects of Baicalein on cell growth, apoptosis, and differentiation. Duolink and IP assay assessed the interaction between HDAC‐1 and ubiquitin, HSP90 and AML1‐ETO, and Ac‐p53 and CBFβ‐MYH11. AML cell lines and primary AML cells‐bearing NOD/SCID mice models were used to evaluate the anti‐leukemic efficiency and potential mechanism of Baicalein in vivo. Results Baicalein showed HDAC‐1/8 inhibition to trigger growth suppression and differentiation induction of AML cell lines and primary AML cells. Although the inhibitory action on HDAC‐1 was mild, Baicalein could induce the degradation of HDAC‐1 via ubiquitin proteasome pathway, thereby upregulating the acetylation of Histone H3 without promoting ABC transporter genes expression. Meanwhile, Baicalein increased the acetylation of HSP90 and lessened its connection to AML1/ETO, consequently leading to degradation of AML1‐ETO in t(8;21)q(22;22) AML cells. In inv(16) AML cells, Baicalein possessed the capacity of apoptosis induction accompanied with p53‐mediated apoptosis genes expression. Moreover, CBFβ‐MYH11‐bound p53 acetylation was restored via HDAC‐8 inhibition induced by Baicalein contributing the diminishing of survival of CD34+ inv(16) AML cells. Conclusions These findings improved the understanding of the epigenetic regulation of Baicalein, and warrant therapeutic potential of Baicalein for CBF‐AML.

show abstract

“…10 It was reported that the incidence of CBFα and CBFβ AML was around 7% and 5–8%, respectively. Although lack of strong epidemiology data, our previous experience 11 and this work proved that, in Chinese population, a slight more CBFα leukemia patients are presented, whereas CBFβ AML are very few.…”

mentioning

confidence: 99%

Kinase-associated gene mutation pattern and clinical relevance in 205 patients with core binding factor leukemias

Wang

et al. 2016

Blood Cancer Journal

View full text Add to dashboard Cite

Beyond KIT in CBF-AML: chromatin and cohesin

Cited by 7 publications

References 10 publications

Core binding factor acute myeloid leukemia: Advances in the heterogeneity of KIT, FLT3, and RAS mutations (Review)

Core binding factor acute myeloid leukemia: Advances in the heterogeneity of KIT, FLT3, and RAS mutations (Review)

Natural HDAC‐1/8 inhibitor baicalein exerts therapeutic effect in CBF‐AML

Kinase-associated gene mutation pattern and clinical relevance in 205 patients with core binding factor leukemias

Contact Info

Product

Resources

About