No abstract

No abstract

Mutated receptor tyrosine kinases (MT-RTKs) such as internal tandem duplication of FMSlike tyrosine kinase 3 (FLT3 ITD) and a point mutation KIT D816V are driver mutations for acute myeloid leukemia (AML). Clathrin assembly lymphoid myeloid leukemia protein (CALM) regulates intracellular transport of RTKs, however, the precise role for MT-RTKs remains elusive. We here show that CALM knock down leads to severely impaired FLT3 ITDor KIT D814V-dependent cell growth compared to marginal influence on wild-type FLT3-or KIT-mediated cell growth. An antipsychotic drug chlorpromazine (CPZ) suppresses the growth of primary AML samples, and human CD34 + CD38-AML cells including AML initiating cells with MT-RTKs in vitro and in vivo. Mechanistically, CPZ reduces CALM protein at post transcriptional level and perturbs the intracellular localization of MT-RTKs, thereby blocking their signaling. Our study presents a therapeutic strategy for AML with MT-RTKs by altering the intracellular localization of MT-RTKs using CPZ.

We report a case with extramedullary tumors affecting the supraclavicular region that presented as a relapse of acute myeloid leukemia (AML) with FLT3-ITD mutation after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Treatment with gilteritinib resulted in remarkable response with disappearance of both the medullary and extramedullary tumors. Subsequently, a 2nd allo-HSCT was performed in an attempt to cure his AML and complete molecular response has been sustained with gilteritinib resumption without worsening GVHD. Targeted therapy with gilteritinib for medullary and extramedullary relapse of FLT3-ITD AML could be effective and suitable as a bridging therapy for allo-HSCT.

An 80-year-old woman experienced dyspnea. Cardiac enlargement was detected by chest radiography at a local hospital. She was admitted to our hospital, and echocardiography and CT revealed pericardial effusion and multiple tumor lesions in right atrium. 18F-FDG PET/CT demonstrated multiple nodular accumulations in these tumors (SUVmax, 14.5). Cytologic analysis of the pericardial fluid revealed a diffuse large B-cell lymphoma. Primary cardiac lymphoma (PCL) is rare, and there are few reports about the 18F-FDG PET/CT imaging features of PCLs. In high 18F-FDG uptake in multiple tumors in the right atrium and large pericardial effusion, a PCL should be considered.