Subtyping of acute myeloid leukemia requires an integration of information from the patient's clinical history (such as any prior preleukemic myeloid neoplasm or cytotoxic potentially leukemogenic therapy), the leukemia morphology, cytogenetic findings, and the mutation status of particular genes (NPM1, FLT3, and CEBPA).
Altogether, these results identified the co-occurrence of mutations in CSF3R and CEBPA in a well-defined AML subset, which uniformly responds to JAK inhibitors and paves the way to personalized clinical trials for this disease.
CEBPA mutations cause a myeloid differentiation block and were detected in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), multiple myeloma and non-Hodgkin's lymphoma (NHL) patients.
+8sole patients were older (p=0.013), presented lower WBC counts (p=0.010), harbored more often ASXL1 mutations (p<0.001) and RUNX1 mutations (p=0.009), but less frequent FLT3-ITD (p=0.038), NPM1 mutations (p<0.001) and double-mutated CEBPA (p=0.038) than NK patients.
The presence of mutations in FLT3 (FMS-like tyrosine kinase 3), NPM1 (Nucleophosmin), and CEBPA (CCAAT/enhancer-binding protein alpha) genes hold prognostic significance in patients with AML and normal cytogenetics.
Mutations of the FLT3, c-KIT, c-FMS, KRAS, NRAS, BRAF and CEBPA genes in the receptor tyrosine kinase (RTK)/RAS-BRAF signal-transduction pathway are frequent in acute myeloid leukemia (AML).
The National Comprehensive Cancer Network (NCCN) defines the following types of acute myeloid leukemia (AML) as favorable-risk: acute promyelocytic leukemia with t(15;17) (APL); AML with core-binding factor (CBF) rearrangements, including t(8;21) and inv(16) or t(16;16) without mutations in KIT (CBF-KIT<sup>wt</sup>); and AML with normal cytogenetics and mutations in NPM1 (NPM1<sup>mut</sup>); or biallelic mutations in CEBPA (CEBPA<sup>mut/mut</sup>), without FLT3-ITD.
Deciphering the mutation spectrum of CEBPAdmAML could facilitate an in-depth understanding of the pathogenesis and refine the prognostic classification of this disease entity.
Newly diagnosed AML patients with normal karyotype who were treated by the Japanese Childhood AML Cooperative Treatment Protocol AML 99 were analyzed in terms of their BAALC expression levels (n = 29), BAALC isoforms (n = 29), and CEBPA mutations (n = 49).
In the present study, we retrospectively analyzed the prognostic significance of CEBPA mutations in 135 AML patients (French-American-British [FAB]-M3 excluded).
CEBPA mutations and polymorphisms were determined in a large series of Southeast Asian AML (n = 247) using polymerase chain reaction and direct sequencing.
Here, we identified a specific subgroup of AML, defined by an expression profile resembling that of AMLs with mutations in the myeloid transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha), while lacking such mutations.
A C-terminal mutant of CCAAT-enhancer-binding protein α (C/EBPα-Cm) downregulates Csf1r, a potent accelerator in the progression of acute myeloid leukemia with C/EBPα-Cm.
We found that mutations in WT1, IDH2, and CEBPA were strongly linked to DNA hypermethylation in AML using a novel integrative analysis of The Cancer Genome Atlas data based on Boolean implications, if-then rules that identify all individual CpG sites that are hypermethylated in the presence of a mutation.
As a result, high HIP1 expression was seen more frequently in older patients, M4/M5 morphology and genes of NPM1 and DNMT3A mutations, and underrepresented in favorable karyotype subgroups and CEBPA double allele mutations in our AML patients.
To explore their impact on this favourable-risk disease, we determined GATA2 status in 153 sporadic AML patients and three members of a germ-line CEBPA-mutant family at AML presentation.
No differences were detected in CEBPA mRNA levels in patients with inv(16) AML-M4Eo (n = 12) compared to patients with AML with a normal karyotype and M4 subtype (n = 6), whereas CEBPA protein and binding activity were significantly reduced in patients with CBFB-SMMHC.