Clinical utility of somatic gene mutation testing in AML and molecular features that may guide treatment strategy and can result in a benefit to patient survival
| Gene . | Clinical utility . |
|---|---|
| NPM1 | Diagnostic, good prognosis in isolation, MRD monitoring |
| FLT3 | ITD confers poorer prognosis, therapeutic target for ITD and TKD |
| CEBPA | Role in diagnosis, familial risk, good prognosis with in-frame bZIP mutation |
| IDH1/2 | Therapeutic targets, proposed role in diagnosis, clonal hematopoiesis |
| TP53 | Very poor prognosis, chemotherapy refractory, may favor hypomethylating agent-based treatment (azacitidine/decitabine) or clinical trial |
| RUNX1 | Poorer prognosis, familial risk |
| KIT | Poorer prognosis in CBF AML, potential therapeutic target |
| TET2 | Associated with clonal hematopoiesis |
| EZH2 | Associated with secondary AML |
| STAG2 | Associated with secondary AML |
| SRSF2 | Associated with secondary AML |
| BCOR | Associated with secondary AML |
| SF3B1 | Associated with secondary AML |
| U2AF1 | Associated with secondary AML |
| ASXL1 | Poor prognosis, secondary AML, clonal hematopoiesis |
| DNMT3A | Associated with clonal hematopoiesis |
| PTPN11 | Associated with clonal hematopoiesis, poorer prognosis |
| Feature | Therapeutic conferring survival advantage |
| FLT3 | (ITD and TKD) midostaurin with induction therapy, gilteritinib at relapse |
| IDH1⁺ | Ivosidinib + azacitidine |
| sAML* | Cytarabine/daunorubicin liposomal (Vyxeos; CPX-351) |
| Gene . | Clinical utility . |
|---|---|
| NPM1 | Diagnostic, good prognosis in isolation, MRD monitoring |
| FLT3 | ITD confers poorer prognosis, therapeutic target for ITD and TKD |
| CEBPA | Role in diagnosis, familial risk, good prognosis with in-frame bZIP mutation |
| IDH1/2 | Therapeutic targets, proposed role in diagnosis, clonal hematopoiesis |
| TP53 | Very poor prognosis, chemotherapy refractory, may favor hypomethylating agent-based treatment (azacitidine/decitabine) or clinical trial |
| RUNX1 | Poorer prognosis, familial risk |
| KIT | Poorer prognosis in CBF AML, potential therapeutic target |
| TET2 | Associated with clonal hematopoiesis |
| EZH2 | Associated with secondary AML |
| STAG2 | Associated with secondary AML |
| SRSF2 | Associated with secondary AML |
| BCOR | Associated with secondary AML |
| SF3B1 | Associated with secondary AML |
| U2AF1 | Associated with secondary AML |
| ASXL1 | Poor prognosis, secondary AML, clonal hematopoiesis |
| DNMT3A | Associated with clonal hematopoiesis |
| PTPN11 | Associated with clonal hematopoiesis, poorer prognosis |
| Feature | Therapeutic conferring survival advantage |
| FLT3 | (ITD and TKD) midostaurin with induction therapy, gilteritinib at relapse |
| IDH1⁺ | Ivosidinib + azacitidine |
| sAML* | Cytarabine/daunorubicin liposomal (Vyxeos; CPX-351) |
bZIP, basic leucine zipper region; CBF, core-binding factor; ITD, internal tandem duplication; MRD, measurable residual disease; TKD, tyrosine kinase domain mutation.
In the phase 3 study comparing azacytidine and venetoclax to azacytidine monotherapy, patients with IDH1 and IDH2 mutations appeared to have improved responses in subgroup analysis.
sAML may be suggested by the finding of high mutation burden and/or EZH2, STAG2, SRSF2, BCOR, RUNX1, SF3B1, U2AF1, and ASXL1, but diagnosis requires correlation with clinical history, morphology, and cytogenetic findings. Vyxeos has shown benefit to patients with sAML.