DNMT3A mutation + FLT3-ITD mutation

The evaluation of NPM1 mut and co-mutation has consistently demonstrated remarkable prognostic significance in AML, suggesting the potential for improved response rates, extended disease-free periods, and OS. Our findings provide valuable insights for understanding molecular leukemogenesis in AML-NK patients and will aid in clinical diagnosis, prognostic implications, and the development of targeted therapy strategies for Syrian AML patients.

The FLT3 inhibitor gilteritinib was administered for reinduction therapy after failure of chemotherapy with a combination of venetoclax, decitabine, aclarubicin, cytarabine and granulocyte colony-stimulating factor. Similar cases of Sweet syndrome following FLT3 inhibitor therapy for acute myeloid leukemia were reviewed. Attention should be given to this rare complication when FLT3 inhibitors are used for acute myeloid leukemia therapy, and appropriate treatments need to be administered in a timely manner.

NRAS mutations were associated with poor outcome in trisomy AML, whereas DNMT3A and FLT3-ITD mutations had neutral effect. Trisomy AML appeared biologically distinct from CN-AML.

RUNX1 was not an independent prognostic factor for survival. Overall, our findings agree with the updated WHO classification system for AML that AML-RUNX1mut should not be recognized as a distinct AML entity.

Patients were treated by an anthracycline and cytarabine-based or homoharringtonine and cytarabine-based induction chemotherapy regimen and followed by high dose cytarabine as consolidation therapy. A<3log reduction of MRD2 was also another independent poor prognostic factor for survival, which could be improved by allo-HSCT. Meanwhile, the conversion of MRD for NPM1 from negative to positive might be a poor prognostic factor, but it requires to be validated by multivariate analysis.

Induction regimens included DA +/- etoposide (ADE) and FLAG-IDA, with or without Gemtuzumab. Conclusion The "triple hit" (NPM1, DNMT3A and FLT3 ITD) genotype, WT1mut and high WCC were associated with poor outcomes, due to a lower probability of achieving MRD–, and a higher relapse risk from MRD– remission. Survival was improved for patients receiving intensified induction with FLAG-Ida including patients in these high-risk groups.

D-CAG regimen is safe and effective in the treatment of AML patients ≥70 years old, and can partially improve the prognosis of elderly and high-risk patients.

Patients with FLT3-ITD and NPM1 mutations have the worst prognosis, where the presence of those mutations was significantly related to overall survival (OS) and EFS. Our study reflects that DNMT3A was not an extremely bad prognostic effect as an independent factor. We can declare according to this study that genetic mutation and variants detection could easily be incorporated into the regimen evaluation of AML patients.

These data suggested PRDM16 expression could be used to predict the outcome of patients with CN-AML. PRDM16 is significantly associated with FLT3-ITD and DNMT3A mutation and WT1 expression and serves as a potential prognostic biomarker in CN-AML.

Our study supports adverse prognostic effect of presence of DNMT3A gene mutation either alone or in the presence of FLT3 and/or NPM1 gene mutations.

In-vitro, Kasumi-1 leukemic cell line, sorted by CD34 expression, showed increased apoptosis only in the CD34 subpopulation after exposure to cytosine arabinoside (Ara-C) or daunorubicin. Interestingly, in these samples, p-ERK levels and apoptosis rates following chemotherapy exposure significantly differed between CD34 populations. Hence, clones may be selected due to their ability to escape apoptosis rather than a direct effect of chemotherapy on a specific mutated clone.

A relatively high mutation frequency is observed in AML patients with 11q23/MLL rearrangements and most cases shows single mutation. The RAS signaling pathway alterations are most common. Gene mutation does not affect the OS of these patients, who show poor prognosis. A significantly higher Hb at initial diagnosis in FLT3 mutated patients is significantly higher than that in FLT3 wild-type cases. Patients who underwent HSCT show a better prognosis than those only received chemotherapy.

DNMT3A, FLT3-ITD, and NPM1A are frequent mutations in Egyptian AML. FLT3-ITD mutations are frequent in older patients. DNMT3A and FLT3-ITD mutations were associated with an unfavorable prognosis, but the NPM1A mutation has tendency to indicate a good prognosis.