The Clinical impact of PTPN11 mutations in adults with acute myeloid leukemia.
Mansour AlfayezGhayas C IssaKeyur P PatelFeng WangXuemei WangNicholas J ShortJorge E CortesTapan Mahendra KadiaFarhad RavandiSherry PierceRita AssiGuillermo Garcia-ManeroCourtney D Di NardoNaval DaverNaveen PemmarajuHagop KantarjianGautam BorthakurPublished in: Leukemia (2020)
While germline and somatic mutations in the gene PTPN11, encoding a phosphatase which regulates the RAS signaling pathway, are well characterized in children with Noonan syndrome and juvenile myelomonocytic leukemia, less is known about their clinical impact in adults with acute myeloid leukemia (AML). To elucidate the effect of PTPN11 mutations (PTPN11mut) on clinical outcomes, we screened adult patients with AML treated at our institution using targeted next-generation sequencing. Among 1406 consecutive patients, 112 (8%) had PTPN11mut. These mutations were more commonly associated with the acute myelomonocytic/monocytic leukemia subtype than was wild-type PTPN11, while none were detected in patients with core-binding factor AML. They co-occurred more commonly with NPM1 mutations and FLT3 internal tandem duplications and less commonly with mutations in IDH2 and a complex karyotype. Compared with the wild-type allele, PTPN11mut was associated with lower complete response rates (54% vs 40%; P = 0.04), and shorter overall survival (median 13.6 vs 8.4 months; P = 0.008). In a multivariate analysis, PTPN11mut independently increased the risk of death, with a hazard ratio of 1.69 (95% CI, 1.25-2.29; P = 0.0007). In summary, mutations in PTPN11 have a characteristic phenotype in adults with AML and are associated with an adverse prognosis.
Keyphrases
- acute myeloid leukemia
- wild type
- allogeneic hematopoietic stem cell transplantation
- signaling pathway
- end stage renal disease
- chronic kidney disease
- gene expression
- young adults
- dna methylation
- emergency department
- peritoneal dialysis
- ejection fraction
- dna repair
- cell proliferation
- oxidative stress
- acute lymphoblastic leukemia
- prognostic factors
- cancer therapy
- high grade
- data analysis
- circulating tumor