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

2021 ◽  
Vol 14 (8) ◽  
pp. e243615
Author(s):  
Samer Alkassis ◽  
Aliza Rizwan ◽  
Lina Daoud ◽  
Jie Chi

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

Blood ◽  
2014 ◽  
Vol 123 (6) ◽  
pp. 905-913 ◽  
Author(s):  
Erika K. Keeton ◽  
Kristen McEachern ◽  
Keith S. Dillman ◽  
Sangeetha Palakurthi ◽  
Yichen Cao ◽  
...  

Key Points AZD1208 is a selective pan-Pim kinase inhibitor with efficacy in AML cells, xenografts, and Flt3-internal tandem duplication or Flt3 wild-type patient samples. AML cell growth inhibition is associated with suppression of p70S6K, 4EBP1 phosphorylation, and messenger RNA translation.


2007 ◽  
Vol 42 (3) ◽  
pp. 250 ◽  
Author(s):  
Sang-Ho Kim ◽  
Yeo-Kyeoung Kim ◽  
Il-Kwon Lee ◽  
Deog-Yeon Jo ◽  
Jong-Ho Won ◽  
...  

Author(s):  
Yuxuan Luo ◽  
Ying Lu ◽  
Bing Long ◽  
Yansi Lin ◽  
Yanling Yang ◽  
...  

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.


Blood ◽  
2011 ◽  
Vol 118 (2) ◽  
pp. 409-412 ◽  
Author(s):  
Claire L. Green ◽  
Catherine M. Evans ◽  
Lu Zhao ◽  
Robert K. Hills ◽  
Alan K. Burnett ◽  
...  

Abstract We have investigated the prognostic significance of isocitrate dehydrogenase 2 (IDH2) mutations in 1473 younger adult acute myeloid leukemia patients treated in 2 United Kingdom Medical Research Council trials. An IDH2 mutation was present in 148 cases (10%), 80% at R140 and 20% at R172. Patient characteristics and outcome differed markedly between the 2 mutations. IDH2R140 significantly correlated with nucleophosmin mutations (NPM1MUT), whereas IDH2R172 cases generally lacked other molecular mutations. An IDH2R140 mutation was an independent favorable prognostic factor for relapse (P = .004) and overall survival (P = .008), and there was no significant heterogeneity with regard to NPM1 or FLT3 internal tandem duplication (FLT3/ITD) genotype. Relapse in FLT3/ITDWTNPM1MUTIDH2R140 patients was lower than in favorable-risk cytogenetics patients in the same cohort (20% and 38% at 5 years, respectively). The presence of an IDH2R172 mutation was associated with a significantly worse outcome than IDH2R140, and relapse in FLT3/ITDWTNPM1WTIDH2R172 patients was comparable with adverse-risk cytogenetics patients (76% and 72%, respectively).


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