Midostaurin-induced Sweet syndrome in a patient with FLT3-ITD-positive AML

Sweet syndrome (SS), also referred as acute febrile neutrophilic dermatosis, is an inflammatory process characterised by the abrupt appearance of erythematous papules or nodules with predominant neutrophilic infiltration in the dermis. Fever and neutrophilia are common presenting features. However, extracellular manifestations, including ocular and musculoskeletal, may occur. SS is divided into three subtypes: classical (or idiopathic), malignancy associated and drug induced. Medication-induced subtype accounts for up to 26% of cases. In recent years, emerging evidence has showed that SS may also occur in neutropenic patients who underwent induction for acute myeloid leukemia (AML). The identification of FMS-like tyrosine kinase 3 (FLT3) gene mutation in approximately 30% of patients with AML has promoted the targeted therapy with FLT3-internal tandem duplication (ITD) inhibitors. Midostaurin, a recently Food and Drug Administration-approved medication for FLT3-ITD-positive AML, was reported once as cause for SS. We report a midostaurin-induced SS with neutropenia in a patient following induction chemotherapy of AML

Blocking DNA Damage Repair May Be Involved in Stattic (STAT3 Inhibitor)-Induced FLT3-ITD AML Cell Apoptosis

The FMS-like tyrosine kinase 3 (FLT3)- internal tandem duplication (ITD) mutation can be found in approximately 25% of all acute myeloid leukemia (AML) cases and is associated with a poor prognosis. The main treatment for FLT3-ITD-positive AML patients includes genotoxic therapy and FLT3 inhibitors, which are rarely curative. Inhibiting STAT3 activity can improve the sensitivity of solid tumor cells to radiotherapy and chemotherapy. This study aimed to explore whether Stattic (a STAT3 inhibitor) affects FLT3-ITD AML cells and the underlying mechanism. Stattic can inhibit the proliferation, promote apoptosis, arrest cell cycle at G0/G1, and suppress DNA damage repair in MV4-11cells. During the process, through mRNA sequencing, we found that DNA damage repair-related mRNA are also altered during the process. In summary, the mechanism by which Stattic induces apoptosis in MV4-11cells may involve blocking DNA damage repair machineries.