Compared with the parental human AMLFLT3-ITD-expressing MOLM13, MOLM13-TKIR cells resistant to AC220 were markedly more sensitive to JQ1-induced apoptosis.
Deregulation of apoptosis is one of the important features of AML and to understand the molecular mechanism underlying apoptosis and its contribution to tumor progression, this study aimed to evaluate anti-apoptotic Bcl2 protein expression in AML and correlate with FLT3 parameters for their role in prognosis of disease.Bcl2 and FLT3 protein expression was quantified by flow cytometry on leukemic blasts in total 174 de novo AML, myelodysplastic syndrome (MDS) and aplastic anemia patients.
Concordant acute myeloblastic leukemia in monozygotic twins with germline and shared somatic mutations in the gene for CCAAT-enhancer-binding protein α with 13 years difference at onset.
CCAAT/enhancer-binding protein alpha (C/EBPalpha) is mutated in 10% of acute myeloid leukemias, resulting in either a truncated protein or an altered leucine zipper (C/EBPalphaLZ) that prevents DNA binding.
All results indicate that synergism exists between FLT3 and NF-κB inhibitors, and inhibitors combination treatment may be a potential strategy for AML.
Here, we describe a Japanese family in which two individuals with acute myeloid leukemia (AML) and one healthy individual had an identical 4-base pair insertion in the N-terminal region of CEBPA (350_351insCTAC), resulting in the termination at codon 107 (I68fsX107).
FLT3 inhibitors are being developed as targeted therapy for FLT3-ITD(+) acute myeloid leukemia; however, their use is complicated by rapid development of resistance, which illustrates the need for additional therapeutic targets.
Here, we describe a Japanese family in which two individuals with acute myeloid leukemia (AML) and one healthy individual had an identical 4-base pair insertion in the N-terminal region of CEBPA (350_351insCTAC), resulting in the termination at codon 107 (I68fsX107).
Overall, these results support the investigation of ponatinib in patients with FLT3-ITD-driven AML and other hematologic malignancies driven by KIT, FGFR1, or PDGFRα.
CEBPA mutation status was not demonstrated to be of prognostic importance in this patient group, although this may reflect the selection and size of the AML population studied.
Interestingly, additional members in the families of both of these patients have been affected by AML, and the germline CEBPA mutations were also observed in these patients.