FOXO1, a member of the evolutionarily conserved forkhead family of transcription factors, regulates expression of a number of genes that play critical roles in cell cycle and apoptosis. A pivotal regulatory mechanism of FOXO is reversible phosphorylation, catalyzed by kinases and phosphatases. Phosphorylation of FOXO1 is associated with 14-3-3 binding and cytosolic localization, whereas dephosphorylated FOXO1 translocates to the nucleus and is transcriptionally active. Experiments were performed to identify the serine/threonine

Noonan syndrome (NS) patients are at increased risk for developing juvenile myelomonocytic leukemia (JMML), an aggressive clonal disorder of aberrant cell proliferation. Many NS patients exhibit spontaneously remitting monocytosis and transient myeloproliferation. The distinction between bone marrow hyperproliferation due to germline mutation and leukemia resulting from clonal transformation can be difficult in NS patients. The GM-CSF hypersensitivity assay, diagnostic of sporadic JMML, can be positive in NS patients at baseline. In this report, we demonstrate the utility of determining the clonal status of the monocyte population by the HUMARA assay in distinguishing JMML and benign myeloproliferation in female NS patients.