To the Editor Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm of childhood with nearly half of all patients relapsing within 3 years [1,2]. More than 90% of JMML patients present with initiating mutations in NF1, KRAS, NRAS, RRAS, RRAS2, CBL, and PTPN11, all leading to hyperactivation of the Ras pathway [3]. Patients with additional molecular alterations including cytogenetic abnormalities, and in particular, point mutations in SETBP1 have inferior outcomes [4]. At present, hematopoietic stem cell transplantation (HSCT) is the only curative therapy, with the primary cause of death being relapse or progression to acute myeloid leukemia (AML) [5]. Recently, JMML patients who did not display Ras pathway mutations were found to have ALK and ROS1 fusions that were sensitive to ALK inhibition [6]. Given the poor overall survival of JMML patients even after intensive treatments such as HSCT, opportunities to implement precision medicine should be

A novel digital PCR (dPCR) platform combining off-the-shelf reagents, a micro-molded plastic microfluidic consumable with a fully integrated single dPCR instrument was developed to address the needs for routine clinical diagnostics. This new platform offers a simplified workflow that enables: rapid time-to-answer; low potential for cross contamination; minimal sample waste; all within a single integrated instrument. Here we showcase the capability of this fully integrated platform to detect and quantify non-small cell lung carcinoma (NSCLC) rare genetic mutants (EGFR T790M) with precision cell-free DNA (cfDNA) standards. Next, we validated the platform with an established chronic myeloid leukemia (CML) fusion gene (BCR-ABL1) assay down to 0.01% mutant allele frequency to highlight the platform’s utility for precision cancer monitoring. Thirdly, using a juvenile myelomonocytic leukemia (JMML) patient-specific assay we demonstrate the ability to precisely track an individual cancer patient’s response to therapy and show the patient’s achievement of complete molecular remission. These three applications highlight the flexibility and utility of this novel fully integrated dPCR platform that has the potential to transform personalized medicine for cancer recurrence monitoring.